Paradiso Angelo Virgilio, Patruno Margherita, Digennaro Maria, Tommasi Stefania, Pilato Brunella, Argentiero Antonella, Brunetti Oronzo, Silvestris Nicola
Experimental Oncology-Center for the Study of Hereditary Cancers, IRCCS-Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Scientific Direction, IRCCS-Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Front Oncol. 2020 Aug 12;10:1292. doi: 10.3389/fonc.2020.01292. eCollection 2020.
BRCA-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk of developing other malignancies including cholangiocarcinoma (CCA). Somatic BRCA mutations have been reported in CCA, but they have yet to be utilized in a proband case to identify HBOC in families. Two healthy daughters of a deceased female patient who had had metachronous breast cancer and CCA received genetic counseling to assess their cancer risk. Somatic mutation analysis was performed by next-generation sequencing on the DNA extracted from a formalin-fixed, paraffin-embedded CCA biopsy specimen of their mother. A pathogenic variant was identified (c.6468_6469delTC in a BRCA2 gene mutation). Germline BRCA mutation analysis of the two daughters detected the same pathogenic variant in one of them. For the first time, a CCA somatic BRCA mutation has been used to identify a family with HBOC.
与BRCA相关的遗传性乳腺癌和卵巢癌综合征（HBOC）的特征是患包括胆管癌（CCA）在内的其他恶性肿瘤的风险增加。CCA中已报道了体细胞BRCA突变，但尚未在先证者病例中用于识别家族性HBOC。一名已故女性患者曾患异时性乳腺癌和CCA，其两名健康女儿接受了遗传咨询，以评估她们患癌风险。对从其母亲的福尔马林固定、石蜡包埋的CCA活检标本中提取的DNA进行了二代测序，以进行体细胞突变分析。鉴定出一个致病变体（BRCA2基因突变中的c.6468_6469delTC）。对两名女儿进行的种系BRCA突变分析在其中一人中检测到相同的致病变体。首次利用CCA体细胞BRCA突变识别出一个HBOC家族。
