Hospital Sirio Libanes, Sao Paulo, Brazil.
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
BMC Cancer. 2017 Sep 5;17(1):623. doi: 10.1186/s12885-017-3599-4.
Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America.
Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome.
We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet.
The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.
遗传咨询和检测林奇综合征（LS）最近已在几个拉丁美洲国家推出。我们旨在描述拉丁美洲疑似 LS 患者的临床、分子和错配修复（MMR）变异谱。
使用 11 个 LS 遗传性癌症登记处和 34 个已发表的 LS 数据库，鉴定符合阿姆斯特丹 II（AMSII）标准和/或贝塞斯达指南的无关家族，或提示显性结直肠（CRC）遗传综合征。
我们对 15 个国家进行了彻底调查，确定了 6 个国家提供 LS 的种系基因检测，3 个国家在 LS 诊断中使用肿瘤检测。致病性 MMR 变异谱包括 MLH1 高达 54%、MSH2 高达 43%、MSH6 高达 10%、PMS2 高达 3%和 EPCAM 高达 0.8%。拉丁美洲 MMR 谱广泛，共有 220 种不同的变异，其中 80%为私有，20%为复发性。常见区域包括 MLH1 的外显子 11（15%）、MSH2 的外显子 3 和 7（分别为 17%和 15%）、MSH6 的外显子 4（65%）、PMS2 的外显子 11 和 13（分别为 31%和 23%）。鉴定出 16 种 MLH1、MSH2 和 MSH6 的国际创始变体，其中 41 种（19%）变体以前没有报道过，因此代表 MMR 基因中的新遗传变体。AMSII 标准是最常用于识别致病性 MMR 携带者的临床标准，尽管微卫星不稳定性、免疫组织化学和家族史仍然是几个尚未提供 LS 基因检测的国家的主要方法。
拉丁美洲 LS 致病性 MMR 变异谱包括新的变异、频繁改变的遗传区域和潜在的创始效应，强调了在所有拉丁美洲国家实施林奇综合征基因检测和咨询的重要性。
