Candidate genes for hereditary colorectal cancer: Mutational screening and systematic review.,Human Mutation

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Candidate genes for hereditary colorectal cancer: Mutational screening and systematic review.
Human Mutation ( IF 3.3 ) Pub Date : 2020-05-25 , DOI: 10.1002/humu.24057
Sami Belhadj _{1,

2} , Mariona Terradas _{1,

2} , Pau M Munoz-Torres _{1,

2} , Gemma Aiza _{1,

2,

3} , Matilde Navarro _{1,

2,

3} , Gabriel Capellá _{1,

2,

3} , Laura Valle _{1,

2,

3}

Affiliation

Genome‐wide approaches applied for the identification of new hereditary colorectal cancer (CRC) genes, identified several potential causal genes, including RPS20, IL12RB1, LIMK2, POLE2, MRE11, POT1, FAN1, WIF1, HNRNPA0, SEMA4A, FOCAD, PTPN12, LRP6, POLQ, BLM, MCM9, and the epigenetic inactivation of PTPRJ. Here we attempted to validate the association between variants in these genes and nonpolyposis CRC by performing a mutational screening of the genes and PTPRJ promoter methylation analysis in 473 familial/early‐onset CRC cases, a systematic review of the published cases, and assessment of allele frequencies in control population. In the studied cohort, 24 (5%) carriers of (predicted) deleterious variants in the studied genes and no constitutional PTPRJ epimutations were identified. Assessment of allele frequencies in controls compared with familial/early‐onset patients with CRC showed association with increased nonpolyposis CRC risk of disruptive variants in RPS20, IL12RB1, POLE2, MRE11 and POT1, and of FAN1 c.149T>G (p.Met50Arg). Lack of association was demonstrated for LIMK2, PTPN12, LRP6, PTPRJ, POLQ, BLM, MCM9 and FOCAD variants. Additional studies are required to provide conclusive evidence for SEMA4A, WIF1, HNRNPA0 c.−110G>C, and FOCAD large deletions.

中文翻译：

遗传性结直肠癌的候选基因：突变筛查和系统评价。

基因组范围的办法应用于新遗传性结直肠癌（CRC）的基因，鉴定确定了几个潜在的因果基因，包括RPS20，IL12RB1，LIMK2，POLE2，MRE11，POT1，FAN1，WIF1，HNRNPA0，SEMA4A，FOCAD，PTPN12，LRP6，POLQ，BLM，MCM9和的后生灭活PTPRJ. 在这里，我们试图通过对473 例家族性/早发性 CRC 病例进行基因突变筛查和PTPRJ启动子甲基化分析、对已发表病例的系统回顾和等位基因评估来验证这些基因变异与非息肉性 CRC 之间的关联。控制人群中的频率。在所研究的队列中，发现了 24 (5%) 名研究基因中（预测的）有害变异的携带者，并且没有鉴定出构成性PTPRJ表观突变。与家族性/早发性 CRC 患者相比，对照中的等位基因频率评估显示，与非息肉病性 CRC 风险增加相关，RPS20、IL12RB1、POLE2、MRE11 中的破坏性变异和POT1，以及FAN1 c.149T>G (p.Met50Arg)。LIMK2、PTPN12、LRP6、PTPRJ、POLQ、BLM、MCM9和FOCAD变体缺乏关联。需要额外的研究来为SEMA4A、WIF1、HNRNPA0 c.-110G>C 和FOCAD大缺失提供确凿证据。

更新日期：2020-05-25

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