Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
BMC Med Genet. 2011 Oct 11;12:134. doi: 10.1186/1471-2350-12-134.
Germline mutations in either of the two tumor-suppressor genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast and ovarian cancer cases. Most of these mutations consist of deletions, insertions, nonsense mutations, and splice variants, however an increasing number of large genomic rearrangements have been identified in these genes.
We analysed BRCA1 and BRCA2 genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the BRCA1 deletion by Array CGH.
We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a de novo complete BRCA1 gene deletion in the germinal line. The detected deletion started from the region surrounding the VAT1 locus to the beginning of NBR1 gene, including the RND2, ΨBRCA1, BRCA1 and NBR2 complete genes.
This finding supports the large genomic rearrangement screening of BRCA genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.
BRCA1 和 BRCA2 这两个肿瘤抑制基因中的任何一个发生种系突变，都会导致相当一部分遗传性乳腺癌和卵巢癌病例。这些突变大多为缺失、插入、无义突变和剪接变异，但在这些基因中已经发现越来越多的大片段基因组重排。
我们通过直接测序和 MLPA 分析 BRCA1 和 BRCA2 基因。我们通过另一种 MLPA 试剂盒确认了结果，并通过 Array CGH 对 BRCA1 缺失进行了特征描述。
我们描述了首例无明显家族病史的患者，该患者在年轻时双侧乳腺癌，种系中存在新出现的完全 BRCA1 基因缺失。检测到的缺失从 VAT1 基因座周围区域开始，到 NBR1 基因起始端，包括 RND2、ΨBRCA1、BRCA1 和 NBR2 完整基因。
这一发现支持对无家族史的年轻乳腺癌患者以及先前其他突变检测阴性的遗传性乳腺癌和卵巢癌家族进行 BRCA 基因大片段重排筛查。
