Yanus Grigoriy A, Akhapkina Tatiana A, Iyevleva Aglaya G, Kornilov Alexandr V, Suspitsin Evgeny N, Kuligina Ekaterina Sh, Ivantsov Alexandr O, Aleksakhina Svetlana N, Sokolova Tatiana N, Sokolenko Anna P, Togo Alexandr V, Imyanitov Evgeny N
St.-Petersburg Pediatric Medical University, 194100, Russia; N.N. Petrov Institute of Oncology, 197758, Russia.
N.N. Petrov Institute of Oncology, 197758, Russia.
Eur J Med Genet. 2020 Mar;63(3):103753. doi: 10.1016/j.ejmg.2019.103753. Epub 2019 Sep 3.
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome (LS), is a common cancer-predisposing syndrome. This study aimed to investigate the spectrum of germ-line mutations in Russian LS patients. LS-related mismatch repair (MMR) genes were analyzed in 16 patients, who were forwarded to genetic testing due to strong clinical features of LS and had high-level microsatellite instability (MSI-H) in the tumor (n = 14) or unknown MSI status (n = 2). In addition, 672 consecutive colorectal cancer (CRC) cases were screened for family history; 15 patients were younger than 50 years and reported 2 or more instances of LS-related cancers in 1st- or 2nd-degree relatives. Seven of these cases demonstrated MSI-H and therefore were subjected to DNA germ-line testing. Overall, 17/23 (74%) subjects carried LS-associated gene variants (MLH1: 10; MSH2: 4; MSH6: 2; PMS2: 1), with 2 alleles (MLH1 c.677G > T and MSH2 с.1906G > C) detected twice. Testing for recurrent mutations of 30 consecutive MSI-H CRCs led to the identification of 2 additional subjects with LS. The analysis of all relevant publications identified 28 unrelated LS patients presented in Russian medical literature and 3 unrelated Russian LS subjects described in international journals. Overall, 15/49 (31%) genetic defects revealed in Russian LS patients were represented by six recurrent alleles (MLH1: c.350C > T, c.677G > T, c.1852_1854del; MSH2: c.942+3A > T, c.1861C > T, с.1906G > C). We conclude that the founder effect for LS in Russia is seemingly less pronounced than the one for hereditary breast-ovarian cancer syndrome, however testing for recurrent LS mutations may be considered feasible in some circumstances.
遗传性非息肉病性结直肠癌（HNPCC），也称为林奇综合征（LS），是一种常见的癌症易感综合征。本研究旨在调查俄罗斯LS患者种系突变的情况。对16例患者的LS相关错配修复（MMR）基因进行了分析，这些患者因具有强烈的LS临床特征而被转诊进行基因检测，且肿瘤具有高水平微卫星不稳定性（MSI-H）（n = 14）或微卫星不稳定性状态未知（n = 2）。此外，对672例连续的结直肠癌（CRC）病例进行了家族史筛查；15例患者年龄小于50岁，且报告一级或二级亲属中有2例或更多例LS相关癌症。其中7例病例显示为MSI-H，因此进行了DNA种系检测。总体而言，17/23（74%）的受试者携带LS相关基因变异（MLH1：10例；MSH2：4例；MSH6：2例；PMS2：1例），有2个等位基因（MLH1 c.677G>T和MSH2 с.1906G>C）被检测到两次。对30例连续的MSI-H CRC进行复发性突变检测，又发现了2例LS患者。对所有相关出版物的分析确定，俄罗斯医学文献中报道了28例无关的LS患者，国际期刊中描述了3例无关的俄罗斯LS受试者。总体而言，俄罗斯LS患者中发现的15/49（31%）的基因缺陷由六个复发性等位基因代表（MLH1：c.350C>T、c.677G>T、c.1852_1854del；MSH2：c.942+3A>T、c.1861C>T、с.1906G>C）。我们得出结论，俄罗斯LS的奠基者效应似乎不如遗传性乳腺癌-卵巢癌综合征明显，然而在某些情况下，对LS复发性突变进行检测可能是可行的。
