Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast and ovarian cancer syndrome (HBOC). Mutations in these genes are usually inherited, and reports of de novo BRCA1/2 mutations are rare. To date, only one patient with low-level BRCA1 mutation mosaicism has been published. We report on a breast cancer patient with constitutional somatic mosaicism of a BRCA2 mutation. BRCA2 mutation c.9294C>G, p.(Tyr3098Ter) was detected in 20% of reads in DNA extracted from peripheral blood using next-generation sequencing (NGS). The BRCA2 mutation was subsequently observed at similar levels in normal breast tissue, adipose tissue, normal right fallopian tube tissue and ovaries of the patient, suggesting that this mutation occurred early in embryonic development. This is the first case to report constitutional mosaicism for a BRCA2 mutation and shows that BRCA2 mosaicism can underlie early-onset breast cancer. NGS for BRCA1/2 should be considered for patients whose tumors harbor a BRCA1/2 mutation and for individuals suggestive of genetic predisposition but without a family history of HBO.

中文翻译：

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BRCA2突变的体质镶嵌术可导致早发性乳腺癌。

BRCA1和BRCA2基因中的种系突变会导致遗传性乳腺癌和卵巢癌综合症（HBOC）。这些基因中的突变通常是遗传的，从头报道BRCA1 / 2突变的报道很少。迄今为止，仅公布了一名患有低水平BRCA1突变镶嵌症的患者。我们报道了一名患有BRCA2突变体质镶嵌的乳腺癌患者。使用下一代测序（NGS）从外周血中提取的DNA的20％读数中检测到BRCA2突变c.9294C> G，p。（Tyr3098Ter）。该BRCA2随后在患者的正常乳腺组织，脂肪组织，正常的右输卵管组织和卵巢中以相似的水平观察到这种突变，表明该突变发生在胚胎发育的早期。这是第一个报道BRCA2突变的结构性镶嵌的病例，表明BRCA2镶嵌性可以成为早发乳腺癌的基础。对于肿瘤携带BRCA1 / 2突变的患者以及暗示遗传易感性但无HBO家族史的患者，应考虑使用NGS for BRCA1 / 2。