Frequent somatic loss of BRCA1 in breast tumours from BRCA2 germ-line mutation carriers and vice versa.
Frequent somatic loss of BRCA1 in breast tumours from BRCA2 germ-line mutation carriers and vice versa.
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DOI：
10.1054/bjoc.2001.2062
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发表时间：
2001-10-19
影响因子：
8.8
通讯作者：
Tanner MM
中科院分区：
文献类型：
--
作者：
Staff S;Isola JJ;Johannsson O;Borg A;Tanner MM
乳腺癌易感基因BRCA 1和BRCA 2是肿瘤抑制基因，其等位基因必须在肿瘤发生之前失活。与BRCA 1和BRCA 2基因的生殖系突变相关的遗传性乳腺癌几乎总是在各自的基因座上显示等位基因不平衡（AI）。BRCA 1和BRCA 2被认为参与维持细胞中基因组完整性的共同途径。我们进行了AI和荧光原位杂交（FISH）分析BRCA 2在乳腺肿瘤生殖系BRCA 1突变携带者，反之亦然。为了比较，还研究了14例散发性乳腺肿瘤。11例BRCA 1突变肿瘤中有8例（73%）在BRCA 2位点显示AI。这些肿瘤中有53%通过FISH显示BRCA 2基因的拷贝数丢失。5/6例（83%）BRCA 2突变肿瘤在BRCA 1位点显示AI。一半的肿瘤（4/8）通过FISH显示BRCA 1基因的物理缺失。BRCA 1和BRCA 2基因的等位基因丢失见于17例信息性遗传性肿瘤中的12例（71%），而两种BRCA基因的拷贝数丢失见于FISH研究的散发性对照肿瘤中的4/14例（29%）。总之，BRCA 2突变肿瘤中BRCA 1的AI高患病率，反之亦然，表明在其他乳腺癌易感基因位点发生的体细胞事件可能在癌症发展中被选择。在这些位点导致AI的机制似乎比物理缺失更复杂。 http://www.bjcancer.com © 2001癌症研究运动
Breast cancer susceptibility genes BRCA1 and BRCA2 are tumour suppressor genes the alleles of which have to be inactivated before tumour development occurs. Hereditary breast cancers linked to germ-line mutations of BRCA1 and BRCA2 genes almost invariably show allelic imbalance (AI) at the respective loci. BRCA1 and BRCA2 are believed to take part in a common pathway in maintenance of genomic integrity in cells. We carried out AI and fluorescence in situ hybridization (FISH) analyses of BRCA2 in breast tumours from germ-line BRCA1 mutation carriers and vice versa. For comparison, 14 sporadic breast tumours were also studied. 8 of the 11 (73%) informative BRCA1 mutation tumours showed AI at the BRCA2 locus. 53% of these tumours showed a copy number loss of the BRCA2 gene by FISH. 5 of the 6 (83%) informative BRCA2 mutation tumours showed AI at the BRCA1 locus. Half of the tumours (4/8) showed a physical deletion of the BRCA1 gene by FISH. Combined allelic loss of both BRCA1 and BRCA2 gene was seen in 12 of the 17 (71%) informative hereditary tumours, whereas copy number losses of both BRCA genes was seen in only 4/14 (29%) sporadic control tumours studied by FISH. In conclusion, the high prevalence of AI at BRCA1 in BRCA2 mutation tumours and vice versa suggests that somatic events occurring at the other breast cancer susceptibility gene locus may be selected in the cancer development. The mechanism resulting in AI at these loci seems more complex than a physical deletion. http://www.bjcancer.com © 2001 Cancer Research Campaign