新发BRCA1基因突变的低水平体质性嵌合现象。
Low-level constitutional mosaicism of a de novoBRCA1 gene mutation.
作者信息
Friedman E, Efrat N, Soussan-Gutman L, Dvir A, Kaplan Y, Ekstein T, Nykamp K, Powers M, Rabideau M, Sorenson J, Topper S
机构信息
1] The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center at Tel-Hashomer, Tel-Aviv 5262100, Israel [2] Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 5262100, Israel.
Department of Oncology, Kaplan Medical Center, Rehovot, Israel.
出版信息
Br J Cancer. 2015 Feb 17;112(4):765-8. doi: 10.1038/bjc.2015.14. Epub 2015 Jan 29.
BACKGROUND
Pathogenic BRCA1 mutations are usually inherited. Constitutional low-level BRCA1 mosaicism has never been reported.
METHODS
Next-generation sequencing (NGS) of cancer gene panel of germline and tumour DNA in a patient with early onset, triple-negative breast cancer.
RESULTS
Constitutional de novo mosaicism (5%) for a pathogenic (c.1953dupG; p.Lys652Glufs*21) BRCA1mutation was detected in leukocytes, buccal tissue and normal breast tissue DNA, with ∼50% mutation in tumorous breast tissue.
CONCLUSION
This is the first reported case of low-level, multiple tissue, constitutional mosaicism in BRCA1, and highlights the need to consider deep sequencing in affected individuals clinically suspected of having cancer predisposition whose tumours display a BRCA mutation.
背景
致病性BRCA1突变通常是遗传性的。从未报道过先天性低水平BRCA1嵌合体。
方法
对一名早发性三阴性乳腺癌患者的生殖系和肿瘤DNA进行癌症基因panel的二代测序（NGS）。
结果
在白细胞、颊黏膜组织和正常乳腺组织DNA中检测到致病性（c.1953dupG；p.Lys652Glufs*21）BRCA1突变的先天性新发嵌合体（5%），肿瘤性乳腺组织中约有50%的突变。
结论
这是首次报道的BRCA1低水平、多组织、先天性嵌合体病例，并强调对于临床上怀疑有癌症易感性且其肿瘤显示BRCA突变的个体，需要考虑进行深度测序。
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