Skip to main content

Advertisement

SpringerLink
Log in

Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis

  • Original Article
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Multigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statement Committee and leadership. A literature search was conducted to address these questions. Recommendations were based on the best available evidence and expert opinion. This position statement addresses which genes should be included on a multigene panel for a patient with a suspected hereditary CRC or polyposis syndrome, proposes updated genetic testing criteria, discusses testing approaches for patients with mismatch repair proficient or deficient CRC, and outlines the essential elements for ordering and disclosing multigene panel test results. We acknowledge that critical gaps in access, insurance coverage, resources, and education remain barriers to high-quality, equitable care for individuals and their families at increased risk of hereditary CRC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DK (2014) Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am J Gastroenterol 109(8):1159–1179. https://doi.org/10.1038/ajg.2014.186

    Article  PubMed  Google Scholar 

  2. Stoffel EM, Koeppe E, Everett J, Ulintz P, Kiel M, Osborne J, Williams L, Hanson K, Gruber SB, Rozek LS (2017) Germline genetic features of young individuals with colorectal cancer. Gastroenterology. https://doi.org/10.1053/j.gastro.2017.11.004

    Article  PubMed  Google Scholar 

  3. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, American College of G (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110(2):223–262. https://doi.org/10.1038/ajg.2014.435

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gupta S, Provenzale D, Llor X, Halverson AL, Grady W, Chung DC, Haraldsdottir S, Markowitz AJ, Slavin TP Jr, Hampel H, Cgc NRM, Weiss JM, Ahnen DJ, Chen LM, Cooper G, Early DS, Giardiello FM, Hall MJ, Hamilton SR, Kanth P, Klapman JB, Lazenby AJ, Lynch PM, Mayer RJ, Mikkelson J, Cgc PS, Regenbogen SE, Dwyer MA, Cgc ON (2019) NCCN Guidelines Insights: genetic/familial high-risk assessment: colorectal, version 2.2019. J Natl Compr Cancer Netw 17(9):1032–1041. https://doi.org/10.6004/jnccn.2019.0044

    Article  Google Scholar 

  5. Tomlinson I, Jaeger E, Leedham S, Thomas H (2013) Reply to "The classification of intestinal polyposis". Nat Genet 45(1):2–3. https://doi.org/10.1038/ng.2475

    Article  CAS  PubMed  Google Scholar 

  6. Daly MB, Pilarski R, Berry M, Buys SS, Farmer M, Friedman S, Garber JE, Kauff ND, Khan S, Klein C, Kohlmann W, Kurian A, Litton JK, Madlensky L, Merajver SD, Offit K, Pal T, Reiser G, Shannon KM, Swisher E, Vinayak S, Voian NC, Weitzel JN, Wick MJ, Wiesner GL, Dwyer M, Darlow S (2017) NCCN Guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Cancer Netw 15(1):9–20

    Article  CAS  Google Scholar 

  7. Gupta S, Provenzale D, Regenbogen SE, Hampel H, Slavin TP Jr, Hall MJ, Llor X, Chung DC, Ahnen DJ, Bray T, Cooper G, Early DS, Ford JM, Giardiello FM, Grady W, Halverson AL, Hamilton SR, Klapman JB, Larson DW, Lazenby AJ, Lynch PM, Markowitz AJ, Mayer RJ, Ness RM, Samadder NJ, Shike M, Sugandha S, Weiss JM, Dwyer MA, Ogba N (2017) NCCN guidelines insights: genetic/familial high-risk assessment: colorectal, version 3.2017. J Natl Compr Cancer Netw 15(12):1465–1475. https://doi.org/10.6004/jnccn.2017.0176

    Article  CAS  Google Scholar 

  8. Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, Comeras I, La Jeunesse J, Nakagawa H, Westman JA, Prior TW, Clendenning M, Penzone P, Lombardi J, Dunn P, Cohn DE, Copeland L, Eaton L, Fowler J, Lewandowski G, Vaccarello L, Bell J, Reid G, de la Chapelle A (2006) Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 66(15):7810–7817. https://doi.org/10.1158/0008-5472.CAN-06-1114

    Article  CAS  PubMed  Google Scholar 

  9. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Clendenning M, Sotamaa K, Prior T, Westman JA, Panescu J, Fix D, Lockman J, LaJeunesse J, Comeras I, de la Chapelle A (2008) Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol 26(35):5783–5788. https://doi.org/10.1200/JCO.2008.17.5950

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352(18):1851–1860. https://doi.org/10.1056/NEJMoa043146

    Article  CAS  PubMed  Google Scholar 

  11. Hampel H, Panescu J, Lockman J, Sotamaa K, Fix D, Comeras I, LaJeunesse J, Nakagawa H, Westman JA, Prior TW, Clendenning M, de la Chapelle A, Frankel W, Penzone P, Cohn DE, Copeland L, Eaton L, Fowler J, Lombardi J, Dunn P, Bell J, Reid G, Lewandowski G, Vaccarello L (2007) Comment on: Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 67(19):9603. https://doi.org/10.1158/0008-5472.CAN-07-2308

    Article  CAS  PubMed  Google Scholar 

  12. Ring KL, Bruegl AS, Allen BA, Elkin EP, Singh N, Hartman AR, Daniels MS, Broaddus RR (2016) Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort. Mod Pathol 29(11):1381–1389. https://doi.org/10.1038/modpathol.2016.135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S (2017) Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol 35(10):1086–1095. https://doi.org/10.1200/JCO.2016.71.0012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, De La Chapelle A, Mecklin JP (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118(5):829–834

    Article  CAS  PubMed  Google Scholar 

  15. Boursi B, Sella T, Liberman E, Shapira S, David M, Kazanov D, Arber N, Kraus S (2013) The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews. Eur J Cancer 49(17):3680–3685. https://doi.org/10.1016/j.ejca.2013.06.040

    Article  CAS  PubMed  Google Scholar 

  16. Liang J, Lin C, Hu F, Wang F, Zhu L, Yao X, Wang Y, Zhao Y (2013) APC polymorphisms and the risk of colorectal neoplasia: a HuGE review and meta-analysis. Am J Epidemiol 177(11):1169–1179. https://doi.org/10.1093/aje/kws382

    Article  PubMed  Google Scholar 

  17. Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, Buchanan DD, Clendenning M, Rosty C, Ahnen DJ, Thibodeau SN, Casey G, Gallinger S, Le Marchand L, Haile RW, Potter JD, Zheng Y, Lindor NM, Newcomb PA, Hopper JL, MacInnis RJ (2017) Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomarkers Prev 26(3):404–412. https://doi.org/10.1158/1055-9965.EPI-16-0693

    Article  CAS  PubMed  Google Scholar 

  18. Sutcliffe EG, Bartenbaker Thompson A, Stettner AR, Marshall ML, Roberts ME, Susswein LR, Wang Y, Klein RT, Hruska KS, Solomon BD (2019) Multi-gene panel testing confirms phenotypic variability in MUTYH-Associated Polyposis. Fam Cancer. https://doi.org/10.1007/s10689-018-00116-2

    Article  PubMed  Google Scholar 

  19. Cheadle JP, Sampson JR (2007) MUTYH-associated polyposis–from defect in base excision repair to clinical genetic testing. DNA Repair (Amst) 6(3):274–279. https://doi.org/10.1016/j.dnarep.2006.11.001

    Article  CAS  Google Scholar 

  20. Win AK, Dowty JG, Cleary SP, Kim H, Buchanan DD, Young JP, Clendenning M, Rosty C, MacInnis RJ, Giles GG, Boussioutas A, Macrae FA, Parry S, Goldblatt J, Baron JA, Burnett T, Le Marchand L, Newcomb PA, Haile RW, Hopper JL, Cotterchio M, Gallinger S, Lindor NM, Tucker KM, Winship IM, Jenkins MA (2014) Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology 146(5):1208–1211. https://doi.org/10.1053/j.gastro.2014.01.022

    Article  CAS  PubMed  Google Scholar 

  21. Howe JR, Sayed MG, Ahmed AF, Ringold J, Larsen-Haidle J, Merg A, Mitros FA, Vaccaro CA, Petersen GM, Giardiello FM, Tinley ST, Aaltonen LA, Lynch HT (2004) The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet 41(7):484–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, Mangold E, Stern M, Knaebel HP, Sutter C, Weber RG, Pistorius S, Burger B, Propping P (2002) Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet 111(1):108–111. https://doi.org/10.1007/s00439-002-0748-9

    Article  CAS  PubMed  Google Scholar 

  23. Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, Mitchell G, Drouin E, Westermann CJ, Marchuk DA (2004) A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 363(9412):852–859. https://doi.org/10.1016/S0140-6736(04)15732-2

    Article  CAS  PubMed  Google Scholar 

  24. Chow E, Lipton L, Carvajal-Carmona LG, Arthur G, Bhathal P, Kaur G, Jaeger E, Woodford-Richens K, Howarth K, Tomlinson I, Macrae F (2007) A family with juvenile polyposis linked to the BMPR1A locus: cryptic mutation or closely linked gene? J Gastroenterol Hepatol 22(12):2292–2297. https://doi.org/10.1111/j.1440-1746.2007.04989.x

    Article  CAS  PubMed  Google Scholar 

  25. Heald B, Mester J, Rybicki L, Orloff MS, Burke CA, Eng C (2010) Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers. Gastroenterology 139(6):1927–1933. https://doi.org/10.1053/j.gastro.2010.06.061

    Article  CAS  PubMed  Google Scholar 

  26. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA (2000) Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology 119(6):1447–1453

    Article  CAS  PubMed  Google Scholar 

  27. Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, Goldberg RM, Paskett E, Shields PG, Freudenheim JL, Stanich PP, Lattimer I, Arnold M, Liyanarachchi S, Kalady M, Heald B, Greenwood C, Paquette I, Prues M, Draper DJ, Lindeman C, Kuebler JP, Reynolds K, Brell JM, Shaper AA, Mahesh S, Buie N, Weeman K, Shine K, Haut M, Edwards J, Bastola S, Wickham K, Khanduja KS, Zacks R, Pritchard CC, Shirts BH, Jacobson A, Allen B, de la Chapelle A, Hampel H, Ohio Colorectal Cancer Prevention Initiative Study G (2017) Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol 3(4):464–471. https://doi.org/10.1001/jamaoncol.2016.5194

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S (2015) Identification of a variety of mutations in cancer predisposition genes in patients with suspected Lynch syndrome. Gastroenterology 149(3):604–613. https://doi.org/10.1053/j.gastro.2015.05.006

    Article  CAS  PubMed  Google Scholar 

  29. Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF (2005) Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97(11):813–822. https://doi.org/10.1093/jnci/dji141

    Article  CAS  PubMed  Google Scholar 

  30. AlDubayan SH, Giannakis M, Moore ND, Han GC, Reardon B, Hamada T, Mu XJ, Nishihara R, Qian Z, Liu L, Yurgelun MB, Syngal S, Garraway LA, Ogino S, Fuchs CS, Van Allen EM (2018) Inherited DNA-repair defects in colorectal cancer. Am J Hum Genet 102(3):401–414. https://doi.org/10.1016/j.ajhg.2018.01.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Consortium CBCC-C (2004) CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74(6):1175–1182. https://doi.org/10.1086/421251

    Article  Google Scholar 

  32. Cybulski C, Gorski B, Huzarski T, Masojc B, Mierzejewski M, Debniak T, Teodorczyk U, Byrski T, Gronwald J, Matyjasik J, Zlowocka E, Lenner M, Grabowska E, Nej K, Castaneda J, Medrek K, Szymanska A, Szymanska J, Kurzawski G, Suchy J, Oszurek O, Witek A, Narod SA, Lubinski J (2004) CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 75(6):1131–1135. https://doi.org/10.1086/426403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Suchy J, Cybulski C, Wokolorczyk D, Oszurek O, Gorski B, Debniak T, Jakubowska A, Gronwald J, Huzarski T, Byrski T, Dziuba I, Gogacz M, Wisniowski R, Wandzel P, Banaszkiewicz Z, Kurzawski G, Kladny J, Narod SA, Lubinski J (2010) CHEK2 mutations and HNPCC-related colorectal cancer. Int J Cancer 126(12):3005–3009. https://doi.org/10.1002/ijc.25003

    Article  CAS  PubMed  Google Scholar 

  34. Yurgelun MB, Masciari S, Joshi VA, Mercado RC, Lindor NM, Gallinger S, Hopper JL, Jenkins MA, Buchanan DD, Newcomb PA, Potter JD, Haile RW, Kucherlapati R, Syngal S, Colon Cancer Family R (2015) Germline TP53 mutations in patients with early-onset colorectal cancer in the Colon Cancer Family Registry. JAMA Oncol 1(2):214–221. https://doi.org/10.1001/jamaoncol.2015.0197

    Article  PubMed  Google Scholar 

  35. MacFarland SP, Zelley K, Long JM, McKenna D, Mamula P, Domchek SM, Nathanson KL, Brodeur GM, Rustgi AK, Katona BW, Maxwell KN (2019) Earlier colorectal cancer screening may be necessary in patients with Li–Fraumeni syndrome. Gastroenterology 156(1):273–274. https://doi.org/10.1053/j.gastro.2018.09.036

    Article  PubMed  Google Scholar 

  36. Jaeger E, Leedham S, Lewis A, Segditsas S, Becker M, Cuadrado PR, Davis H, Kaur K, Heinimann K, Howarth K, East J, Taylor J, Thomas H, Tomlinson I (2012) Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet 44(6):699–703. https://doi.org/10.1038/ng.2263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rohlin A, Eiengard F, Lundstam U, Zagoras T, Nilsson S, Edsjo A, Pedersen J, Svensson J, Skullman S, Karlsson BG, Bjork J, Nordling M (2016) GREM1 and POLE variants in hereditary colorectal cancer syndromes. Genes Chromosomes Cancer 55(1):95–106. https://doi.org/10.1002/gcc.22314

    Article  CAS  PubMed  Google Scholar 

  38. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Guarino E, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S, Consortium C, Consrtium WGS, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJ, McVean G, Houlston RS, Tomlinson I (2013) Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 45(2):136–144. https://doi.org/10.1038/ng.2503

    Article  CAS  PubMed  Google Scholar 

  39. Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P (2004) Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 74(5):1043–1050. https://doi.org/10.1086/386293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Weren RD, Ligtenberg MJ, Kets CM, de Voer RM, Verwiel ET, Spruijt L, van Zelst-Stams WA, Jongmans MC, Gilissen C, Hehir-Kwa JY, Hoischen A, Shendure J, Boyle EA, Kamping EJ, Nagtegaal ID, Tops BB, Nagengast FM, Geurts van Kessel A, van Krieken JH, Kuiper RP, Hoogerbrugge N (2015) A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet 47(6):668–671. https://doi.org/10.1038/ng.3287

    Article  CAS  PubMed  Google Scholar 

  41. Grolleman JE, de Voer RM, Elsayed FA, Nielsen M, Weren RDA, Palles C, Ligtenberg MJL, Vos JR, Ten Broeke SW, de Miranda N, Kuiper RA, Kamping EJ, Jansen EAM, Vink-Borger ME, Popp I, Lang A, Spier I, Huneburg R, James PA, Li N, Staninova M, Lindsay H, Cockburn D, Spasic-Boskovic O, Clendenning M, Sweet K, Capella G, Sjursen W, Hoberg-Vetti H, Jongmans MC, Neveling K, Geurts van Kessel A, Morreau H, Hes FJ, Sijmons RH, Schackert HK, Ruiz-Ponte C, Dymerska D, Lubinski J, Rivera B, Foulkes WD, Tomlinson IP, Valle L, Buchanan DD, Kenwrick S, Adlard J, Dimovski AJ, Campbell IG, Aretz S, Schindler D, van Wezel T, Hoogerbrugge N, Kuiper RP (2019) Mutational signature analysis reveals NTHL1 deficiency to cause a multi-tumor phenotype. Cancer Cell 35(2):256–266. https://doi.org/10.1016/j.ccell.2018.12.011

    Article  CAS  PubMed  Google Scholar 

  42. Adam R, Spier I, Zhao B, Kloth M, Marquez J, Hinrichsen I, Kirfel J, Tafazzoli A, Horpaopan S, Uhlhaas S, Stienen D, Friedrichs N, Altmuller J, Laner A, Holzapfel S, Peters S, Kayser K, Thiele H, Holinski-Feder E, Marra G, Kristiansen G, Nothen MM, Buttner R, Moslein G, Betz RC, Brieger A, Lifton RP, Aretz S (2016) Exome sequencing identifies biallelic MSH3 germline mutations as a recessive subtype of colorectal adenomatous polyposis. Am J Hum Genet 99(2):337–351. https://doi.org/10.1016/j.ajhg.2016.06.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Guda K, Moinova H, He J, Jamison O, Ravi L, Natale L, Lutterbaugh J, Lawrence E, Lewis S, Willson JK, Lowe JB, Wiesner GL, Parmigiani G, Barnholtz-Sloan J, Dawson DW, Velculescu VE, Kinzler KW, Papadopoulos N, Vogelstein B, Willis J, Gerken TA, Markowitz SD (2009) Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc Natl Acad Sci USA 106(31):12921–12925. https://doi.org/10.1073/pnas.0901454106

    Article  PubMed  PubMed Central  Google Scholar 

  44. Nieminen TT, O'Donohue MF, Wu Y, Lohi H, Scherer SW, Paterson AD, Ellonen P, Abdel-Rahman WM, Valo S, Mecklin JP, Jarvinen HJ, Gleizes PE, Peltomaki P (2014) Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency. Gastroenterology 147(3):595–598. https://doi.org/10.1053/j.gastro.2014.06.009

    Article  CAS  PubMed  Google Scholar 

  45. Kadouri L, Hubert A, Rotenberg Y, Hamburger T, Sagi M, Nechushtan C, Abeliovich D, Peretz T (2007) Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations. J Med Genet 44(7):467–471. https://doi.org/10.1136/jmg.2006.048173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lin KM, Ternent CA, Adams DR, Thorson AG, Blatchford GJ, Christensen MA, Watson P, Lynch HT (1999) Colorectal cancer in hereditary breast cancer kindreds. Dis Colon Rectum 42(8):1041–1045

    Article  CAS  PubMed  Google Scholar 

  47. Phelan CM, Iqbal J, Lynch HT, Lubinski J, Gronwald J, Moller P, Ghadirian P, Foulkes WD, Armel S, Eisen A, Neuhausen SL, Senter L, Singer CF, Ainsworth P, Kim-Sing C, Tung N, Llacuachaqui M, Chornokur G, Ping S, Narod SA, Hereditary Breast Cancer Study G (2014) Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: results from a follow-up study. Br J Cancer 110(2):530–534. https://doi.org/10.1038/bjc.2013.741

    Article  CAS  PubMed  Google Scholar 

  48. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68(3):700–710. https://doi.org/10.1086/318787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sopik V, Phelan C, Cybulski C, Narod SA (2015) BRCA1 and BRCA2 mutations and the risk for colorectal cancer. Clin Genet 87(5):411–418. https://doi.org/10.1111/cge.12497

    Article  CAS  PubMed  Google Scholar 

  50. Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S, Bernards SS, Casadei S, Yi Q, Burger RA, Chan JK, Davidson SA, Mannel RS, DiSilvestro PA, Lankes HA, Ramirez NC, King MC, Swisher EM, Birrer MJ (2016) Inherited mutations in women with ovarian carcinoma. JAMA Oncol 2(4):482–490. https://doi.org/10.1001/jamaoncol.2015.5495

    Article  PubMed  PubMed Central  Google Scholar 

  51. Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King MC, Swisher EM (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci USA 108(44):18032–18037. https://doi.org/10.1073/pnas.1115052108

    Article  PubMed  PubMed Central  Google Scholar 

  52. Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS (2016) Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med 375(5):443–453. https://doi.org/10.1056/NEJMoa1603144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL, Sharma L, Saam J, Lancaster J, Daly MB (2017) A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer 123(10):1721–1730. https://doi.org/10.1002/cncr.30498

    Article  CAS  PubMed  Google Scholar 

  54. Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, Olson JE, Godwin AK, Pankratz VS, Olswold C, Slettedahl S, Hallberg E, Guidugli L, Davila JI, Beckmann MW, Janni W, Rack B, Ekici AB, Slamon DJ, Konstantopoulou I, Fostira F, Vratimos A, Fountzilas G, Pelttari LM, Tapper WJ, Durcan L, Cross SS, Pilarski R, Shapiro CL, Klemp J, Yao S, Garber J, Cox A, Brauch H, Ambrosone C, Nevanlinna H, Yannoukakos D, Slager SL, Vachon CM, Eccles DM, Fasching PA (2015) Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 33(4):304–311. https://doi.org/10.1200/JCO.2014.57.1414

    Article  CAS  PubMed  Google Scholar 

  55. Cancer Genome Atlas Research Network. Electronic address aadhe, Cancer Genome Atlas Research N (2017) Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 32(2):185–203. https://doi.org/10.1016/j.ccell.2017.07.007

    Article  CAS  Google Scholar 

  56. Grant RC, Selander I, Connor AA, Selvarajah S, Borgida A, Briollais L, Petersen GM, Lerner-Ellis J, Holter S, Gallinger S (2015) Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. Gastroenterology 148(3):556–564. https://doi.org/10.1053/j.gastro.2014.11.042

    Article  CAS  PubMed  Google Scholar 

  57. Shindo K, Yu J, Suenaga M, Fesharakizadeh S, Cho C, Macgregor-Das A, Siddiqui A, Witmer PD, Tamura K, Song TJ, Navarro Almario JA, Brant A, Borges M, Ford M, Barkley T, He J, Weiss MJ, Wolfgang CL, Roberts NJ, Hruban RH, Klein AP, Goggins M (2017) Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol 35(30):3382–3390. https://doi.org/10.1200/JCO.2017.72.3502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ (2018) Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA 319(23):2401–2409. https://doi.org/10.1001/jama.2018.6228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96(4):261–268

    Article  CAS  PubMed  Google Scholar 

  60. Balmana J, Balaguer F, Castellvi-Bel S, Steyerberg EW, Andreu M, Llor X, Jover R, Castells A, Syngal S, Gastrointestinal Oncology Group of the Spanish Gastroenterological A (2008) Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients. J Med Genet 45(9):557–563. https://doi.org/10.1136/jmg.2008.059311

    Article  CAS  PubMed  Google Scholar 

  61. Green RC, Parfrey PS, Woods MO, Younghusband HB (2009) Prediction of Lynch syndrome in consecutive patients with colorectal cancer. J Natl Cancer Inst 101(5):331–340. https://doi.org/10.1093/jnci/djn499

    Article  PubMed  Google Scholar 

  62. Kastrinos F, Uno H, Ukaegbu C, Alvero C, McFarland A, Yurgelun MB, Kulke MH, Schrag D, Meyerhardt JA, Fuchs CS, Mayer RJ, Ng K, Steyerberg EW, Syngal S (2017) Development and validation of the PREMM5 model for comprehensive risk assessment of Lynch syndrome. J Clin Oncol 35(19):2165–2172. https://doi.org/10.1200/JCO.2016.69.6120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kastrinos F, Uno H, Syngal S (2018) Commentary: PREMM5 threshold of 2.5% is recommended to improve identification of PMS2 carriers. Fam Cancer. https://doi.org/10.1007/s10689-018-0074-6

    Article  PubMed  Google Scholar 

  64. Evaluation of Genomic Applications in P, Prevention Working G (2009) Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genet Med 11(1):15–20. https://doi.org/10.1097/GIM.0b013e31818efd9d

    Article  CAS  Google Scholar 

  65. Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN (2009) EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med 11(1):42–65

    Article  PubMed  PubMed Central  Google Scholar 

  66. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520. https://doi.org/10.1056/NEJMoa1500596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Grover S, Kastrinos F, Steyerberg EW, Cook EF, Dewanwala A, Burbidge LA, Wenstrup RJ, Syngal S (2012) Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA 308(5):485–492. https://doi.org/10.1001/jama.2012.8780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Stanich PP, Pearlman R, Hinton A, Gutierrez S, LaDuca H, Hampel H, Jasperson K (2018) Prevalence of germline mutations in polyposis and colorectal cancer-associated genes in patients with multiple colorectal polyps. Clin Gastroenterol Hepatol. https://doi.org/10.1016/j.cgh.2018.12.008

    Article  PubMed  Google Scholar 

  69. Aaltonen LA, Jarvin H, Gruber SB, Billaud M, Jass JR (2000) Peutz-Jeghers syndrome. In: Hamilton SR, Aaltonen LA (eds) Tumors of the digestive system. Lyon, France, pp 74–76

    Google Scholar 

  70. Giardiello FM, Hamilton SR, Kern SE, Offerhaus GJ, Green PA, Celano P, Krush AJ, Booker SV (1991) Colorectal neoplasia in juvenile polyposis or juvenile polyps. Arch Dis Child 66(8):971–975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Snover DC (2010) Serrated polyps of the colon and rectum and serrated polyposis. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system. WHO, Geneva, pp 160–165

    Google Scholar 

  72. Taupin D, Lam W, Rangiah D, McCallum L, Whittle B, Zhang Y, Andrews D, Field M, Goodnow CC, Cook MC (2015) A deleterious RNF43 germline mutation in a severely affected serrated polyposis kindred. Hum Genome Var 2:15013. https://doi.org/10.1038/hgv.2015.13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. International society for gastrointestinal hereditary tumours-InSiGHT (2017). Fam Cancer 16(1):1–134. https://doi.org/10.1007/s10689-017-0026-6

  74. Guarinos C, Juarez M, Egoavil C, Rodriguez-Soler M, Perez-Carbonell L, Salas R, Cubiella J, Rodriguez-Moranta F, de-Castro L, Bujanda L, Serradesanferm A, Nicolas-Perez D, Herraiz M, Fernandez-Banares F, Herreros-de-Tejada A, Aguirre E, Balmana J, Rincon ML, Pizarro A, Polo-Ortiz F, Castillejo A, Alenda C, Paya A, Soto JL, Jover R (2014) Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps. Clin Cancer Res 20(5):1158–1168. https://doi.org/10.1158/1078-0432.CCR-13-1490

    Article  CAS  PubMed  Google Scholar 

  75. Morak M, Heidenreich B, Keller G, Hampel H, Laner A, de la Chapelle A, Holinski-Feder E (2014) Biallelic MUTYH mutations can mimic Lynch syndrome. Eur J Hum Genet 22(11):1334–1337. https://doi.org/10.1038/ejhg.2014.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Castillejo A, Vargas G, Castillejo MI, Navarro M, Barbera VM, Gonzalez S, Hernandez-Illan E, Brunet J, Ramon y Cajal T, Balmana J, Oltra S, Iglesias S, Velasco A, Solanes A, Campos O, Sanchez Heras AB, Gallego J, Carrasco E, GonzalezJuan D, Segura A, Chirivella I, Juan MJ, Tena I, Lazaro C, Blanco I, Pineda M, Capella G, Soto JL (2014) Prevalence of germline MUTYH mutations among Lynch-like syndrome patients. Eur J Cancer 50(13):2241–2250. https://doi.org/10.1016/j.ejca.2014.05.022

    Article  CAS  PubMed  Google Scholar 

  77. Jansen AM, van Wezel T, van den Akker BE, Ventayol Garcia M, Ruano D, Tops CM, Wagner A, Letteboer TG, Gomez-Garcia EB, Devilee P, Wijnen JT, Hes FJ, Morreau H (2016) Combined mismatch repair and POLE/POLD1 defects explain unresolved suspected Lynch syndrome cancers. Eur J Hum Genet 24(7):1089–1092. https://doi.org/10.1038/ejhg.2015.252

    Article  CAS  PubMed  Google Scholar 

  78. Rodriguez-Soler M, Perez-Carbonell L, Guarinos C, Zapater P, Castillejo A, Barbera VM, Juarez M, Bessa X, Xicola RM, Clofent J, Bujanda L, Balaguer F, Rene JM, De-Castro L, Marin-Gabriel JC, Lanas A, Cubiella J, Nicolas-Perez D, Brea-Fernandez A, Castellvi-Bel S, Alenda C, Ruiz-Ponte C, Carracedo A, Castells A, Andreu M, Llor X, Soto JL, Paya A, Jover R (2013) Risk of cancer in cases of suspected lynch syndrome without germline mutation. Gastroenterology 144(5):926–932. https://doi.org/10.1053/j.gastro.2013.01.044

    Article  CAS  PubMed  Google Scholar 

  79. Geurts-Giele WR, Leenen CH, Dubbink HJ, Meijssen IC, Post E, Sleddens HF, Kuipers EJ, Goverde A, van den Ouweland AM, van Lier MG, Steyerberg EW, van Leerdam ME, Wagner A, Dinjens WN (2014) Somatic aberrations of mismatch repair genes as a cause of microsatellite-unstable cancers. J Pathol 234(4):548–559. https://doi.org/10.1002/path.4419

    Article  CAS  PubMed  Google Scholar 

  80. Haraldsdottir S, Hampel H, Tomsic J, Frankel WL, Pearlman R, de la Chapelle A, Pritchard CC (2014) Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology 147(6):1308–1316. https://doi.org/10.1053/j.gastro.2014.08.041

    Article  PubMed  Google Scholar 

  81. Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, Kwint MP, Hoogerbrugge N, Nagtegaal ID, Ligtenberg MJ (2014) Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology 146(3):643–646. https://doi.org/10.1053/j.gastro.2013.12.002

    Article  CAS  PubMed  Google Scholar 

  82. Sourrouille I, Coulet F, Lefevre JH, Colas C, Eyries M, Svrcek M, Bardier-Dupas A, Parc Y, Soubrier F (2013) Somatic mosaicism and double somatic hits can lead to MSI colorectal tumors. Fam Cancer 12(1):27–33. https://doi.org/10.1007/s10689-012-9568-9

    Article  CAS  PubMed  Google Scholar 

  83. Pearlman R, Haraldsdottir S, de la Chapelle A, Jonasson JG, Liyanarachchi S, Frankel WL, Rafnar T, Stefansson K, Pritchard CC, Hampel H (2019) Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome. J Med Genet. https://doi.org/10.1136/jmedgenet-2018-105698

    Article  PubMed  Google Scholar 

  84. American Gastroenterological A (2001) American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing. Gastroenterology 121(1):195–197

    Article  Google Scholar 

  85. National Society of Genetic Counselors' Definition Task F, Resta R, Biesecker BB, Bennett RL, Blum S, Hahn SE, Strecker MN, Williams JL (2006) A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report. J Genet Couns 15(2):77–83. https://doi.org/10.1007/s10897-005-9014-3

    Article  Google Scholar 

  86. Riley BD, Culver JO, Skrzynia C, Senter LA, Peters JA, Costalas JW, Callif-Daley F, Grumet SC, Hunt KS, Nagy RS, McKinnon WC, Petrucelli NM, Bennett RL, Trepanier AM (2012) Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns 21(2):151–161. https://doi.org/10.1007/s10897-011-9462-x

    Article  PubMed  Google Scholar 

  87. Robson ME, Bradbury AR, Arun B, Domchek SM, Ford JM, Hampel HL, Lipkin SM, Syngal S, Wollins DS, Lindor NM (2015) American Society of Clinical Oncology Policy Statement Update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 33(31):3660–3667. https://doi.org/10.1200/JCO.2015.63.0996

    Article  CAS  PubMed  Google Scholar 

  88. Bradbury AR, Patrick-Miller L, Long J, Powers J, Stopfer J, Forman A, Rybak C, Mattie K, Brandt A, Chambers R, Chung WK, Churpek J, Daly MB, Digiovanni L, Farengo-Clark D, Fetzer D, Ganschow P, Grana G, Gulden C, Hall M, Kohler L, Maxwell K, Merrill S, Montgomery S, Mueller R, Nielsen S, Olopade O, Rainey K, Seelaus C, Nathanson KL, Domchek SM (2015) Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility. Genet Med 17(6):485–492. https://doi.org/10.1038/gim.2014.134

    Article  PubMed  Google Scholar 

  89. Bradbury AR, Patrick-Miller LJ, Egleston BL, DiGiovanni L, Brower J, Harris D, Stevens EM, Maxwell KN, Kulkarni A, Chavez T, Brandt A, Long JM, Powers J, Stopfer JE, Nathanson KL, Domchek SM (2016) Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing. Genet Med 18(1):25–33. https://doi.org/10.1038/gim.2015.19

    Article  PubMed  Google Scholar 

  90. Cragun D, Radford C, Dolinsky JS, Caldwell M, Chao E, Pal T (2014) Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory. Clin Genet 86(6):510–520. https://doi.org/10.1111/cge.12359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK (2016) Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med 18(8):823–832. https://doi.org/10.1038/gim.2015.166

    Article  CAS  PubMed  Google Scholar 

  92. Lincoln SE, Yang S, Cline MS, Kobayashi Y, Zhang C, Topper S, Haussler D, Paten B, Nussbaum RL (2017) Consistency of BRCA1 and BRCA2 variant classifications among clinical diagnostic laboratories. JCO Precis Oncol. https://doi.org/10.1200/PO.16.00020

    Article  PubMed  PubMed Central  Google Scholar 

  93. Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC (2016) Improving performance of multigene panels for genomic analysis of cancer predisposition. Genet Med 18(10):974–981. https://doi.org/10.1038/gim.2015.212

    Article  CAS  PubMed  Google Scholar 

  94. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980–985. https://doi.org/10.1093/nar/gkt1113

    Article  CAS  PubMed  Google Scholar 

  95. Balmana J, Digiovanni L, Gaddam P, Walsh MF, Joseph V, Stadler ZK, Nathanson KL, Garber JE, Couch FJ, Offit K, Robson ME, Domchek SM (2016) Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing. J Clin Oncol 34(34):4071–4078. https://doi.org/10.1200/JCO.2016.68.4316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Plazzer JP, Sijmons RH, Woods MO, Peltomaki P, Thompson B, Den Dunnen JT, Macrae F (2013) The InSiGHT database: utilizing 100 years of insights into Lynch syndrome. Fam Cancer 12(2):175–180. https://doi.org/10.1007/s10689-013-9616-0

    Article  CAS  PubMed  Google Scholar 

  97. Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capella G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, Martins A, Moller P, Morak M, Nystrom M, Peltomaki P, Pineda M, Qi M, Ramesar R, Rasmussen LJ, Royer-Pokora B, Scott RJ, Sijmons R, Tavtigian SV, Tops CM, Weber T, Wijnen J, Woods MO, Macrae F, Genuardi M (2014) Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet 46(2):107–115. https://doi.org/10.1038/ng.2854

    Article  CAS  PubMed  Google Scholar 

  98. Herzig DO, Buie WD, Weiser MR, You YN, Rafferty JF, Feingold D, Steele SR (2017) Clinical Practice Guidelines for the Surgical Treatment of Patients With Lynch Syndrome. Dis Colon Rectum 60(2):137–143. https://doi.org/10.1097/DCR.0000000000000785

    Article  PubMed  Google Scholar 

  99. Kalady MF, Church JM (2015) Prophylactic colectomy: rationale, indications, and approach. J Surg Oncol 111(1):112–117. https://doi.org/10.1002/jso.23820

    Article  PubMed  Google Scholar 

  100. You YN, Lakhani VT, Wells SA Jr (2007) The role of prophylactic surgery in cancer prevention. World J Surg 31(3):450–464. https://doi.org/10.1007/s00268-006-0616-1

    Article  PubMed  Google Scholar 

  101. Gallego CJ, Shirts BH, Bennette CS, Guzauskas G, Amendola LM, Horike-Pyne M, Hisama FM, Pritchard CC, Grady WM, Burke W, Jarvik GP, Veenstra DL (2015) Next-generation sequencing panels for the diagnosis of colorectal cancer and polyposis syndromes: a cost-effectiveness analysis. J Clin Oncol 33(18):2084–2091. https://doi.org/10.1200/JCO.2014.59.3665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE (2016) Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol 34(13):1460–1468. https://doi.org/10.1200/JCO.2015.65.0747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The CGA-IGC would like to thank Marian Simonson and Loren Hackett of the Cleveland Clinic for their assistance with the literature search.

Funding

None.

Author information

Authors and Affiliations

  1. Sanford R Weiss, MD, Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, OH, USA

    Brandie Heald & James Church

  2. Division of Human Genetics, Department of Internal Medicine and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    Heather Hampel

  3. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Beth Dudley

  4. Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA

    Michael J. Hall

  5. Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Maureen E. Mork & Y. Nancy You

  6. Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA

    Aparajita Singh

  7. Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    Elena Stoffel

  8. Gastrointestinal Cancer Risk and Prevention Clinic, University of Chicago, Chicago, IL, USA

    Jessica Stoll & Sonia S. Kupfer

  9. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Matthew B. Yurgelun

Authors
  1. Brandie Heald
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heather Hampel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Church
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beth Dudley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael J. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maureen E. Mork
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aparajita Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elena Stoffel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jessica Stoll
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Y. Nancy You
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Matthew B. Yurgelun
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sonia S. Kupfer
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer

Corresponding author

Correspondence to Brandie Heald.

Ethics declarations

Conflict of interest

Dr. Hall has clinical trial support from Merck and Astra Zeneca and research collaborations with Caris, Foundation Medicine, Myriad Genetics Laboratories Inc., Ambry Genetics, and Invitae. Ms. Hampel has performed collaborative research with Ambry Genetics, Invitae, and Myriad Genetic Laboratories Inc., and she is on the scientific advisory boards of Invitae and Genome Medical. She has stock in Genome Medical as an advisory board member. Ms. Heald is on the Speakers Bureau for Myriad Genetics Laboratories Inc. and an advisory board for Invitae. Dr. Yurgelun previously received research funding from Myriad Genetics Laboratories Inc. Ms. Stoll has performed collaborative research with Myriad Genetics Laboratory Inc. and is on an advisory board for Invitae. Dr. Kupfer has performed collaborative research with Myriad Genetics Laboratories Inc. The remaining authors have no potential conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Electronic supplementary material 1 (DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heald, B., Hampel, H., Church, J. et al. Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis. Familial Cancer 19, 223–239 (2020). https://doi.org/10.1007/s10689-020-00170-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-020-00170-9

Keywords

Search

Navigation