Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 1 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea.
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.
Cancer Genet. 2022 Aug;266-267:19-27. doi: 10.1016/j.cancergen.2022.05.042. Epub 2022 May 28.
A significant number of hereditary breast or ovarian cancers are caused by germline variants, mostly BRCA1/BRCA2 genes. Because genetic predispositions vary by ethnicity, several studies have reported founder variants of BRCA1/BRCA2 genes. Such founder variants were reported primarily based on their relevant population frequencies. We reviewed the variant data relating to BRCA1 and BRCA2 genes from January 2012 to March 2019 at Samsung Medical Center, Seoul, Korea. Among the cases with pathogenic variants (PVs) or likely pathogenic variants (LPVs), we defined recurrent variants as those found in more than five unrelated patients. Using single nucleotide polymorphisms, we analyzed patient haplotypes. There were 14 recurrent variants in the BRCA1 gene and seven variants in the BRCA2 gene. Of note, three variants in each gene were primarily detected in Korean populations. Among them, the c.5339T>C (p.Leu1780Pro) BRCA1 variant had a long block sized 74.5 kb. In BRCA2, the c.1399A>T (p.Lys467*) variant had a long block sized 35.5 kb. We suggest that BRCA1 c.5339T>C (p.Leu1780Pro) and BRCA2 c.1399A>T (p.Lys467*) are founder variants of the Korean population. These two recurrent variants were ethnicity-prevalent, primarily found in Korean populations, and the sizes of the linkage disequilibrium blocks are longer than others.
大量遗传性乳腺癌或卵巢癌是由种系变异引起的，主要是 BRCA1/BRCA2 基因。由于遗传易感性因种族而异，因此有几项研究报告了 BRCA1/BRCA2 基因的创始变体。这些创始变体主要是根据其相关人群频率报告的。我们回顾了 2012 年 1 月至 2019 年 3 月在韩国首尔三星医疗中心与 BRCA1 和 BRCA2 基因相关的变异数据。在具有致病性变异（PVs）或可能致病性变异（LPVs）的病例中，我们将反复出现的变异定义为在五个以上无亲缘关系的患者中发现的变异。我们使用单核苷酸多态性分析了患者的单倍型。BRCA1 基因中有 14 个反复出现的变异，BRCA2 基因中有 7 个变异。值得注意的是，每个基因中的三个变异主要在韩国人群中检测到。其中，BRCA1 基因的 c.5339T>C（p.Leu1780Pro）变异有一个 74.5kb 的长块。在 BRCA2 中，c.1399A>T（p.Lys467*）变异有一个 35.5kb 的长块。我们建议 BRCA1 c.5339T>C（p.Leu1780Pro）和 BRCA2 c.1399A>T（p.Lys467*）是韩国人群的创始变体。这两个反复出现的变异是种族流行的，主要在韩国人群中发现，并且连锁不平衡块的大小大于其他变异。
