Cock-Rada A M, Ossa C A, Garcia H I, Gomez L R
Instituto de Cancerologia Las Americas, Medellin, Colombia.
Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.
Fam Cancer. 2018 Jan;17(1):23-30. doi: 10.1007/s10689-017-0004-z.
Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene: BRCA1 (7), BRCA2 (8), PALB2 (1), ATM (1), MSH2 (1) and PMS2 (1). The frequency of mutations in BRCA1/2 was 17.6%. One BRCA2 mutation (c.9246dupG) was recurrent in five non-related individuals and is not previously reported in the country. Seventeen mutation-carriers had a diagnosis of breast cancer (median age of diagnosis of 36 years) and two of ovarian cancer. All BRCA1 mutation-carriers with breast cancer had triple negative tumors (median age of diagnosis of 31 years). Variants of unknown significance were reported in 35% of test results. This is the first report of a multi-gene study for hereditary breast and/or ovarian cancer in a Latin American country. We found a high frequency and a wide spectrum of germline mutations in cancer susceptibility genes in Colombian patients, some of which were not previously reported in the country. We observed a very low frequency of known Colombian founder BRCA1/2 mutations (1.2%) and we found mutations in other genes such as PALB2, ATM, MSH2 and PMS2. Our results highlight the importance of performing multi-gene panel testing, including comprehensive BRCA1/2 analysis (full gene sequencing and large rearrangement analysis), in high-risk breast and/or ovarian cancer patients in Colombia.
BRCA1和BRCA2的种系突变约占遗传性乳腺癌和卵巢癌的50%。在哥伦比亚已报告了BRCA1/2的三种始祖突变，但其他癌症易感基因的突变模式尚不清楚。本研究描述了哥伦比亚一家转诊癌症中心遗传性乳腺癌和/或卵巢癌基因种系突变的频率和类型。分析纳入了85名转诊至麦德林（哥伦比亚）美洲癌症研究所肿瘤遗传学科、符合遗传性乳腺癌和卵巢癌综合征检测标准（NCCN 2015）且接受了商业25基因遗传性癌症检测板种系检测的女性。19名患者（22.4%）在癌症易感基因中携带有害种系突变：BRCA1（7例）、BRCA2（8例）、PALB2（1例）、ATM（1例）、MSH2（1例）和PMS2（1例）。BRCA1/2的突变频率为17.6%。一种BRCA2突变（c.9246dupG）在5名无亲缘关系的个体中反复出现，该国此前未报告过。17名突变携带者被诊断为乳腺癌（诊断中位年龄为36岁），2名被诊断为卵巢癌。所有患乳腺癌的BRCA1突变携带者均为三阴性肿瘤（诊断中位年龄为31岁）。35%的检测结果报告了意义未明的变异。这是拉丁美洲国家关于遗传性乳腺癌和/或卵巢癌多基因研究的首份报告。我们发现哥伦比亚患者癌症易感基因中的种系突变频率高且范围广，其中一些在该国此前未报告过。我们观察到已知的哥伦比亚BRCA1/2始祖突变频率非常低（1.2%），并且我们在其他基因如PALB2、ATM、MSH2和PMS2中发现了突变。我们的结果强调了对哥伦比亚高危乳腺癌和/或卵巢癌患者进行多基因检测板检测的重要性，包括全面的BRCA1/2分析（全基因测序和大片段重排分析）。
