No evidence of involvement of germline BACH1 mutations in Finnish breast and ovarian cancer families
No evidence of involvement of germline BACH1 mutations in Finnish breast and ovarian cancer families
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DOI：
10.1016/s0959-8049(02)00498-7
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发表时间：
2003-02-01
影响因子：
8.4
通讯作者：
Winqvist, R
中科院分区：
文献类型：
--
作者：
Karppinen, SM;Vuosku, J;Winqvist, R
BACH 1是一种定位于染色体17q22的新型DNA解旋酶，与BRCA 1相互作用，可能是乳腺癌和卵巢癌易感基因之一。在这里，我们筛选了来自151个芬兰家庭的214名乳腺癌和卵巢癌患者的生殖系BACH 1突变，利用构象敏感性凝胶电泳（CSGE）和基因组测序分析。在BACH 1的外显子区域中观察到四个序列改变，其中三个先前已报道并被归类为多态性。在1例患者中，观察到一种新的杂合3101 C> T变异体，导致密码子1034处的脯氨酸替换为亮氨酸（Pro1034Leu）。这种氨基酸变化发生在BACH1蛋白的BRCA1结合结构域中。虽然在304名癌症状态未知的对照个体中也发现了3101 C> T转换，但这种改变仍然可能代表人群中罕见的疾病相关等位基因。需要功能测定来解决这种新的BACH 1错义变体的生物学意义。总而言之，现有数据表明BACH 1的生殖系突变非常罕见。(C)2003爱思唯尔科技有限公司版权所有。
Recently BACH1, a novel putative DNA helicase mapping to chromosome 17q22, was reported to interact specifically with BRCA1, and was suggested to be a candidate gene for predisposition to breast and ovarian cancers. Here, we screened 214 breast and ovarian cancer patients from 151 Finnish families for germline BACH1 mutations by utilising conformation-sensitive gel electrophoresis (CSGE) and genomic sequencing analysis. Four sequence alterations were observed in the exon regions of BACH1, three of which have been previously reported and were classified as polymorphisms. In 1 patient, a novel heterozygous 3101C > T variant was observed resulting in a proline to leucine substitution at codon 1034 (Pro1034Leu). This amino acid change occurs in the BRCA1 binding domain of the BACH1 protein. Although the 3101C > T transition was also found in one of the 304 control individuals with an unknown cancer status, it still remains possible that this alteration could represent a rare disease-related allele in the population. Functional assays are needed to resolve the biological significance of this novel BACH1 missense variant. Altogether, the available data suggest that germline mutations in BACH1 are extremely rare. (C) 2003 Elsevier Science Ltd. All rights reserved.