A recent study suggested a role of CHEK2 loss-of-function germ-line pathogenic variants in the predisposition to testicular cancer (TC) (AlDubayan et al. JAMA Oncol 5:514–522, 2019). We attempted to validate this finding relying on the high population frequency of recurrent CHEK2 pathogenic variants in Slavic populations. CHEK2 pathogenic alleles (c.1100delC (p.Thr367Metfs); del5395 [del ex9-10]; IVS2 + 1G > A [c.444 + 1G > A]) were detected in 7/280 (2.5%) TC patients vs. 3/424 (0.7%) healthy men and 6/1007 (0.6%) healthy women [OR 4.0 (95% CI 1.5–11), p = 0.009 for pooled control groups]. Somatic CHEK2 loss-of-heterozygosity (LOH) was detected in 4 out of 6 tumors available for analysis; strikingly all these instances of LOH involved inactivation of the wild-type allele. The CHEK2 c.470T > C (p.Ile157Thr) variant was detected in 21/280 (7.5%) affected vs. 22/424 (5.2%) non-affected men [OR 1.5 (95% CI 0.8–2.7), p = 0.3]. Somatic CHEK2 LOH was revealed only in 6 out of 21 tumors obtained from CHEK2 c.470T > C (p.Ile157Thr) carriers, with the C-allele lost in two cases and T-allele deleted in four tumors. The results of comparison of allele frequencies in TC patients versus population controls coupled with the data on CHEK2 LOH status in tumor tissues support the association of CHEK2 pathogenic variants with TC risk.

最近的一项研究表明CHEK2功能丧失生殖系致病变异在睾丸癌 (TC) 易感性中的作用（AlDubayan 等人，JAMA Oncol 5:514–522, 2019）。我们试图根据斯拉夫人群中复发性CHEK2致病变异的高人群频率来验证这一发现。CHEK2致病等位基因（c.1100delC（p.Thr367Metfs）; del5395 [德尔ex9-10]; IVS2 + 1G> A [c.444 + 1G> A]）在280分之7（2.5％）TC病人对被检测3/424 (0.7%) 健康男性和 6/1007 (0.6%) 健康女性 [OR 4.0 (95% CI 1.5–11)， 合并对照组p = 0.009]。体细胞CHEK2在可供分析的 6 个肿瘤中有 4 个检测到杂合性缺失 (LOH)；引人注目的是，所有这些 LOH 实例都涉及野生型等位基因的失活。的CHEK2在280分之21（7.5％）的影响与424分之22（5.2％）未患病男性[OR 1.5（95％CI 0.8-2.7），检测c.470T> C（p.Ile157Thr）变体p  = 0.3]。从CHEK2 c.470T > C (p.Ile157Thr) 携带者获得的 21 个肿瘤中，仅在 6 个肿瘤中发现体细胞CHEK2 LOH ，其中 C 等位基因在两个病例中丢失，T 等位基因在四个肿瘤中缺失。TC 患者与人群对照等位基因频率的比较结果以及肿瘤组织中CHEK2 LOH 状态的数据支持CHEK2的关联 具有 TC 风险的致病变异。