Germline ATBF1 mutations and prostate cancer risk
Germline ATBF1 mutations and prostate cancer risk
复制标题
DOI：
10.1002/pros.20430
复制
发表时间：
2006-07-01
期刊：
影响因子：
2.8
通讯作者：
Isaacs, William B.
中科院分区：
文献类型：
--
作者：
Xu, Junyan;Sauvageot, Jurga;Isaacs, William B.
背景。ATBF1最近被确定为前列腺肿瘤抑制基因的候选基因。除了更多独特的突变外，在多个前列腺癌样本中都观察到两种体细胞突变(聚嘧啶束缩短[Poly(T)（n)]和从密码子3381 （3381 del）开始的缺失），两者似乎都对ATBF1基因的功能和表达有影响。我们分析了前列腺癌患者和对照组生殖系DNA中两种复发性序列变异，并研究了这些变异的携带者患前列腺癌的风险是否增加。我们在多例患者的正常和匹配肿瘤DNA样本中发现Poly(T)(n)变异，表明每种情况下都有种系起源。种系DNA样本的基因分型显示，在散发病例中，3381del与前列腺癌风险显著相关（P = 0.03），但在有遗传性疾病的男性中则无显著相关性。我们的研究表明生殖系3381del等位基因可能影响前列腺癌的易感性。
BACKGROUND. ATBF1 has been recently identified as a candidate prostate tumor suppressor gene. In addition to more unique mutations, two somatic mutations (shortening of a polypyrimidine tract [Poly(T)(n)] and a deletion beginning at codon 3381 (3381 del)) were each observed in multiple prostate cancer samples and both appear to have an impact on ATBF1 gene function and expression.METHODS. We assayed two recurrent sequence variants in germline DNA from prostate cancer cases and controls, and examined whether carriers of these variants are at increased risk for prostate cancer.RESULTS. We found Poly(T)(n) variants in both normal and matched tumor DNA samples from multiple patients, indicating a germline origin in each case. Genotyping germline DNA samples indicated that 3381del was significantly associated with prostate cancer risk among sporadic cases (P = 0.03), but not among men with hereditary disease.CONCLUSIONS. Our study indicates that the germline 3381del allele may influence prostate cancer susceptibility.