Ishihara Eiko, Matsubayashi Hiroyuki, Nishimura Seiichiro, Isaka Mitsuhiro, Konno Hayato, Goto Seiya, Yamaguchi Ken, Urakami Kenichi
Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan.
Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.
J Obstet Gynaecol Res. 2024 Sep;50(9):1742-1747. doi: 10.1111/jog.16045. Epub 2024 Aug 8.
Pathological germline variants (PGVs) of RAD51D increase the risk of breast and ovarian cancer. In East Asia, c.270_271dup is the most frequently detected PGV of RAD51D; however, only a few cases have been reported in Japan. We report four cancer cases with a germline RAD51D c.270_271dup PGV. Three of them (lung cancer: 2, oral cancer: 1) were incidentally identified by whole genome sequencing in patients negative for the associated cancer histories, homologous recombination (HR) deficiency, or a second hit of RAD51D in the cancer DNA. For genetic counseling, we provided information on surveillance and cascade testing based on Western guidelines. The PGVs of moderate-risk HR-related genes are difficult to detect based on phenotype, especially in male-predominant pedigrees. The current spread of cancer genomic analysis will increase opportunities for incidental variant identification. The establishment of Japanese guidelines is expected to aid in the management of PGV carriers of moderate-risk genes.
RAD51D的病理性种系变异（PGV）会增加患乳腺癌和卵巢癌的风险。在东亚，c.270_271dup是最常检测到的RAD51D的PGV；然而，在日本仅有少数病例报道。我们报告了4例携带种系RAD51D c.270_271dup PGV的癌症病例。其中3例（肺癌：2例，口腔癌：1例）是在无相关癌症病史、同源重组（HR）缺陷或癌症DNA中RAD51D二次打击的患者中通过全基因组测序偶然发现的。为了进行遗传咨询，我们根据西方指南提供了有关监测和级联检测的信息。基于表型很难检测到中度风险HR相关基因的PGV，尤其是在以男性为主的家系中。目前癌症基因组分析的普及将增加偶然发现变异的机会。预计日本指南的制定将有助于对中度风险基因的PGV携带者进行管理。
