Ghimenti Chiara, Sensi Elisa, Presciuttini Silvano, Brunetti Isa Maura, Conte PierFranco, Bevilacqua Generoso, Caligo Maria A
Division of Pathology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Pisa, Italy.
Genes Chromosomes Cancer. 2002 Mar;33(3):235-42. doi: 10.1002/gcc.1223.
BARD1 (BRCA1-associated RING domain) was identified by yeast two-hybrid screening as a protein interacting with BRCA1. Somatic and germline mutations of BARD1 have been detected in sporadic breast, ovarian, and endometrial cancers. The present study represents the first description of BARD1 germline mutations in hereditary breast and breast/ovarian cancer patients. We analyzed the BARD1 gene in 40 families with hereditary breast and breast/ovarian cancer, tested negative for BRCA1 and BRCA2 mutations. A mutational analysis by PCR-SSCP on the coding region and the exon-intron splice boundaries of the BARD1 gene yielded four different germline mutations. A group of 20 patients diagnosed with sporadic breast cancer below the age of 40 was also examined and only one germline mutation was found. A study of loss of heterozygosity at the BARD1 locus in neoplastic tissues from patients with BARD1 germline mutations was carried out. In all cases, we were unable to find any evidence for allelic deletions. The involvement of BARD1 mutations in the susceptibility to hereditary breast and breast/ovarian cancer is discussed.
BARD1（BRCA1相关的环状结构域）通过酵母双杂交筛选被鉴定为一种与BRCA1相互作用的蛋白质。在散发性乳腺癌、卵巢癌和子宫内膜癌中已检测到BARD1的体细胞和种系突变。本研究首次描述了遗传性乳腺癌和乳腺/卵巢癌患者中的BARD1种系突变。我们分析了40个遗传性乳腺癌和乳腺/卵巢癌家族中的BARD1基因，这些家族的BRCA1和BRCA2突变检测均为阴性。通过PCR-SSCP对BARD1基因的编码区和外显子-内含子剪接边界进行突变分析，发现了四种不同的种系突变。对一组20例年龄在40岁以下的散发性乳腺癌患者也进行了检查，仅发现1种种系突变。对具有BARD1种系突变患者的肿瘤组织中BARD1基因座杂合性缺失进行了研究。在所有病例中，我们均未找到任何等位基因缺失的证据。本文讨论了BARD1突变与遗传性乳腺癌和乳腺/卵巢癌易感性的关系。
