Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences I (ICB I), Federal University of Goiás, Goiânia 74690900, Brazil.
Clinical of Hospital (HC), Federal University of Goiás (UFG), Goiânia 74690900, Brazil.
Biomolecules. 2022 Apr 27;12(5):640. doi: 10.3390/biom12050640.
gene mutation is the most common genetic alteration in human malignant tumors and is mainly responsible for Li-Fraumeni syndrome. Among the several cancers related to this syndrome, breast cancer (BC) is the most common. The p.R337H germline pathogenic variant is highly prevalent in Brazil's South and Southeast regions, accounting for 0.3% of the general population. We investigated the prevalence of germline pathogenic variants in a cohort of 83 BC patients from the Midwest Brazilian region. All patients met the clinical criteria for hereditary breast and ovarian cancer syndrome (HBOC) and were negative for and mutations. Moreover, 40 index patients fulfilled HBOC and the Li-Fraumeni-like (LFL) syndromes criteria. The samples were tested using next generation sequencing for . Three patients harbored missense pathogenic variants (p.Arg248Gln, p.Arg337His, and p.Arg337Cys), confirmed by Sanger sequencing. One (1.2%) patient showed a large deletion (exons 2-11), which was also confirmed. The p.R337H variant was detected in only one patient. In conclusion, four (4.8%) early-onset breast cancer patients fulfilling the HBOC and LFL syndromes presented pathogenic variants, confirming the relevance of genetic tests in this group of patients. In contrast to other Brazilian regions, p.R337H variant appeared with low prevalence.
基因突变是人类恶性肿瘤中最常见的遗传改变，主要导致 Li-Fraumeni 综合征。在与该综合征相关的几种癌症中，乳腺癌（BC）最为常见。p.R337H 种系致病性变异在巴西南部和东南部地区非常普遍，占总人口的 0.3%。我们调查了来自巴西中西部地区的 83 例 BC 患者队列中种系致病性变异的流行情况。所有患者均符合遗传性乳腺癌和卵巢癌综合征（HBOC）的临床标准，且为阴性。此外，40 名指数患者符合 HBOC 和 Li-Fraumeni 样（LFL）综合征标准。使用下一代测序对进行了测试。有 3 名患者携带种系错义致病性变异（p.Arg248Gln、p.Arg337His 和 p.Arg337Cys），经 Sanger 测序证实。1 名（1.2%）患者显示出较大的缺失（外显子 2-11），也得到了证实。仅在 1 名患者中检测到 p.R337H 变异。总之，4 名（4.8%）符合 HBOC 和 LFL 综合征的早发性乳腺癌患者存在种系致病性变异，证实了遗传检测在这组患者中的重要性。与巴西其他地区相比，p.R337H 变异的出现频率较低。
