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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-16 , DOI: 10.1038/s41467-019-14100-6 Maria Escala-Garcia,Jean Abraham,Irene L Andrulis,Hoda Anton-Culver,Volker Arndt,Alan Ashworth,Paul L Auer,Päivi Auvinen,Matthias W Beckmann,Jonathan Beesley,Sabine Behrens,Javier Benitez,Marina Bermisheva,Carl Blomqvist,William Blot,Natalia V Bogdanova,Stig E Bojesen,Manjeet K Bolla,Anne-Lise Børresen-Dale,Hiltrud Brauch,Hermann Brenner,Sara Y Brucker,Barbara Burwinkel,Carlos Caldas,Federico Canzian,Jenny Chang-Claude,Stephen J Chanock,Suet-Feung Chin,Christine L Clarke,Fergus J Couch,Angela Cox,Simon S Cross,Kamila Czene,Mary B Daly,Joe Dennis,Peter Devilee,Janet A Dunn,Alison M Dunning,Miriam Dwek,Helena M Earl,Diana M Eccles,A Heather Eliassen,Carolina Ellberg,D Gareth Evans,Peter A Fasching,Jonine Figueroa,Henrik Flyger,Manuela Gago-Dominguez,Susan M Gapstur,Montserrat García-Closas,José A García-Sáenz,Mia M Gaudet,Angela George,Graham G Giles,David E Goldgar,Anna González-Neira,Mervi Grip,Pascal Guénel,Qi Guo,Christopher A Haiman,Niclas Håkansson,Ute Hamann,Patricia A Harrington,Louise Hiller,Maartje J Hooning,John L Hopper,Anthony Howell,Chiun-Sheng Huang,Guanmengqian Huang,David J Hunter,Anna Jakubowska,Esther M John,Rudolf Kaaks,Pooja Middha Kapoor,Renske Keeman,Cari M Kitahara,Linetta B Koppert,Peter Kraft,Vessela N Kristensen,Diether Lambrechts,Loic Le Marchand,Flavio Lejbkowicz,Annika Lindblom,Jan Lubiński,Arto Mannermaa,Mehdi Manoochehri,Siranoush Manoukian,Sara Margolin,Maria Elena Martinez,Tabea Maurer,Dimitrios Mavroudis,Alfons Meindl,Roger L Milne,Anna Marie Mulligan,Susan L Neuhausen,Heli Nevanlinna,William G Newman,Andrew F Olshan,Janet E Olson,Håkan Olsson,Nick Orr,Paolo Peterlongo,Christos Petridis,Ross L Prentice,Nadege Presneau,Kevin Punie,Dhanya Ramachandran,Gad Rennert,Atocha Romero,Mythily Sachchithananthan,Emmanouil Saloustros,Elinor J Sawyer,Rita K Schmutzler,Lukas Schwentner,Christopher Scott,Jacques Simard,Christof Sohn,Melissa C Southey,Anthony J Swerdlow,Rulla M Tamimi,William J Tapper,Manuel R Teixeira,Mary Beth Terry,Heather Thorne,Rob A E M Tollenaar,Ian Tomlinson,Melissa A Troester,Thérèse Truong,Clare Turnbull,Celine M Vachon,Lizet E van der Kolk,Qin Wang,Robert Winqvist,Alicja Wolk,Xiaohong R Yang,Argyrios Ziogas,Paul D P Pharoah,Per Hall,Lodewyk F A Wessels,Georgia Chenevix-Trench,Gary D Bader,Thilo Dörk,Douglas F Easton,Sander Canisius,Marjanka K Schmidt
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-16 , DOI: 10.1038/s41467-019-14100-6 Maria Escala-Garcia,Jean Abraham,Irene L Andrulis,Hoda Anton-Culver,Volker Arndt,Alan Ashworth,Paul L Auer,Päivi Auvinen,Matthias W Beckmann,Jonathan Beesley,Sabine Behrens,Javier Benitez,Marina Bermisheva,Carl Blomqvist,William Blot,Natalia V Bogdanova,Stig E Bojesen,Manjeet K Bolla,Anne-Lise Børresen-Dale,Hiltrud Brauch,Hermann Brenner,Sara Y Brucker,Barbara Burwinkel,Carlos Caldas,Federico Canzian,Jenny Chang-Claude,Stephen J Chanock,Suet-Feung Chin,Christine L Clarke,Fergus J Couch,Angela Cox,Simon S Cross,Kamila Czene,Mary B Daly,Joe Dennis,Peter Devilee,Janet A Dunn,Alison M Dunning,Miriam Dwek,Helena M Earl,Diana M Eccles,A Heather Eliassen,Carolina Ellberg,D Gareth Evans,Peter A Fasching,Jonine Figueroa,Henrik Flyger,Manuela Gago-Dominguez,Susan M Gapstur,Montserrat García-Closas,José A García-Sáenz,Mia M Gaudet,Angela George,Graham G Giles,David E Goldgar,Anna González-Neira,Mervi Grip,Pascal Guénel,Qi Guo,Christopher A Haiman,Niclas Håkansson,Ute Hamann,Patricia A Harrington,Louise Hiller,Maartje J Hooning,John L Hopper,Anthony Howell,Chiun-Sheng Huang,Guanmengqian Huang,David J Hunter,Anna Jakubowska,Esther M John,Rudolf Kaaks,Pooja Middha Kapoor,Renske Keeman,Cari M Kitahara,Linetta B Koppert,Peter Kraft,Vessela N Kristensen,Diether Lambrechts,Loic Le Marchand,Flavio Lejbkowicz,Annika Lindblom,Jan Lubiński,Arto Mannermaa,Mehdi Manoochehri,Siranoush Manoukian,Sara Margolin,Maria Elena Martinez,Tabea Maurer,Dimitrios Mavroudis,Alfons Meindl,Roger L Milne,Anna Marie Mulligan,Susan L Neuhausen,Heli Nevanlinna,William G Newman,Andrew F Olshan,Janet E Olson,Håkan Olsson,Nick Orr,Paolo Peterlongo,Christos Petridis,Ross L Prentice,Nadege Presneau,Kevin Punie,Dhanya Ramachandran,Gad Rennert,Atocha Romero,Mythily Sachchithananthan,Emmanouil Saloustros,Elinor J Sawyer,Rita K Schmutzler,Lukas Schwentner,Christopher Scott,Jacques Simard,Christof Sohn,Melissa C Southey,Anthony J Swerdlow,Rulla M Tamimi,William J Tapper,Manuel R Teixeira,Mary Beth Terry,Heather Thorne,Rob A E M Tollenaar,Ian Tomlinson,Melissa A Troester,Thérèse Truong,Clare Turnbull,Celine M Vachon,Lizet E van der Kolk,Qin Wang,Robert Winqvist,Alicja Wolk,Xiaohong R Yang,Argyrios Ziogas,Paul D P Pharoah,Per Hall,Lodewyk F A Wessels,Georgia Chenevix-Trench,Gary D Bader,Thilo Dörk,Douglas F Easton,Sander Canisius,Marjanka K Schmidt
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Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
中文翻译：
一项网络分析，以确定乳腺癌预后中种系驱动差异的调节因素。
确定乳腺癌预后遗传性的潜在遗传驱动因素仍然难以捉摸。我们采用基于网络的方法来处理动力不足的复杂数据集，从而为生殖系变异在乳腺癌预后中的潜在功能提供新的见解。这项基于网络的分析研究了 84,457 名乳腺癌患者中约 730 万个变异与乳腺癌生存的关系，并在 12,381 名独立患者中证实了结果。通过汇总多个基因的遗传变异对预后的影响，我们确定了与雌激素受体 (ER) 阴性患者的生存相关的四个基因模块和与 ER 阳性疾病的生存相关的一个基因模块。这些模块显示了癌症相关过程的生物富集，例如 G-α 信号传导、生物钟、血管生成和细胞凋亡中的 Rho-GTP 酶。
更新日期：2020-01-16
中文翻译：
一项网络分析，以确定乳腺癌预后中种系驱动差异的调节因素。
确定乳腺癌预后遗传性的潜在遗传驱动因素仍然难以捉摸。我们采用基于网络的方法来处理动力不足的复杂数据集，从而为生殖系变异在乳腺癌预后中的潜在功能提供新的见解。这项基于网络的分析研究了 84,457 名乳腺癌患者中约 730 万个变异与乳腺癌生存的关系，并在 12,381 名独立患者中证实了结果。通过汇总多个基因的遗传变异对预后的影响，我们确定了与雌激素受体 (ER) 阴性患者的生存相关的四个基因模块和与 ER 阳性疾病的生存相关的一个基因模块。这些模块显示了癌症相关过程的生物富集，例如 G-α 信号传导、生物钟、血管生成和细胞凋亡中的 Rho-GTP 酶。
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