来自CONFIRM研究的肾癌病例中ACKR3和COPS8的突变筛查

Mutation screening of ACKR3 and COPS8 in kidney cancer cases from the CONFIRM study.

作者信息

Mahmoodi Maryam, Nguyen-Dumont Tu, Hammet Fleur, Pope Bernard J, Park Daniel J, Southey Melissa C, Darlow John M, Bruinsma Fiona, Winship Ingrid

机构信息

Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.

Victorian Life Sciences Computation Initiative, Melbourne, VIC, 3010, Australia.

出版信息

Fam Cancer. 2017 Jul;16(3):411-416. doi: 10.1007/s10689-016-9961-x.

DOI:10.1007/s10689-016-9961-x

PMID:28063109

Abstract

An apparently balanced t(2;3)(q37.3;q13.2) translocation that appears to segregate with renal cell carcinoma (RCC) has indicated potential areas to search for the elusive genetic basis of clear cell RCC. We applied Hi-Plex targeted sequencing to analyse germline DNA from 479 individuals affected with clear cell RCC for this breakpoint translocation and genetic variants in neighbouring genes on chromosome 2, ACKR3 and COPS8. While only synonymous variants were found in COPS8, one of the missense variants in ACKR3:c.892C>T, observed in 4/479 individuals screened (0.8%), was predicted likely to damage ACKR3 function. Identification of causal genes for RCC has potential clinical utility, where risk assessment and risk management can offer better outcomes, with surveillance for at-risk relatives and nephron sparing surgery through earlier intervention.

摘要

一种明显平衡的t(2;3)(q37.3;q13.2)易位似乎与肾细胞癌（RCC）相关，这表明了寻找透明细胞RCC难以捉摸的遗传基础的潜在区域。我们应用Hi-Plex靶向测序分析了479例受透明细胞RCC影响个体的种系DNA，以检测该断点易位以及2号染色体上邻近基因ACKR3和COPS8中的遗传变异。虽然在COPS8中仅发现同义变异，但在479例筛查个体中有4例（0.8%）观察到ACKR3中的一个错义变异c.892C>T，预计可能损害ACKR3功能。鉴定RCC的致病基因具有潜在的临床应用价值，通过风险评估和风险管理可以提供更好的结果，包括对高危亲属的监测以及通过早期干预进行保留肾单位手术。