Contributions of ATM mutations to familial breast and ovarian cancer.
Contributions of ATM mutations to familial breast and ovarian cancer.
复制标题
DOI：
--
复制
发表时间：
2003-06
期刊：
影响因子：
11.2
通讯作者：
Y. Thorstenson;Adriane Roxas;R. Kroiss;M. Jenkins;Kristine M. Yu;T. Bachrich;D. Muhr;T. Wayne;G. Chu;Ronald W. Davis;T. Wagner;P. Oefner
中科院分区：
文献类型：
--
作者：
Y. Thorstenson;Adriane Roxas;R. Kroiss;M. Jenkins;Kristine M. Yu;T. Bachrich;D. Muhr;T. Wayne;G. Chu;Ronald W. Davis;T. Wagner;P. Oefner
本研究探讨了奥地利家族中ATM突变的患病率及其与乳腺癌的相关性，这些家族选择有乳腺癌或卵巢癌病史或两者兼而有之[遗传性乳腺癌和卵巢癌（HBOC）]。在先前筛查BRCA 1和BRCA 2突变的270个HBOC家族中，确定了137种不同的ATM序列改变。其中7个突变推测会导致共济失调毛细血管扩张症的基础上，他们对ATM蛋白的影响，包括5个，导致蛋白质截短和两个错义突变的催化激酶结构域的高度保守的COOH末端的蛋白质。10个家系（3.7%）发现7种突变。此外，在13个HBOC家族（4.8%）中观察到一种错义变异L1420 F，但在122名无乳腺癌病史的健康志愿者中未观察到。此外，该变异在一些家族中与乳腺癌分离，这表明它可能是乳腺癌的致病性。在65个HBOC家族中观察到62个具有潜在意义的额外变异，但在健康对照中没有观察到。这些变体包括24个序列改变，可能影响剪接或蛋白质-蛋白质相互作用。这项研究表明，在乳腺癌和卵巢癌家族中ATM突变的患病率很高，并且越来越多的证据表明ATM突变增加了乳腺癌的易感性。
This study addresses the prevalence of ATM mutations and the association with breast cancer in Austrian families selected for a history of breast or ovarian cancer or both [hereditary breast and ovarian cancer (HBOC)]. In 270 HBOC families previously screened for BRCA1 and BRCA2 mutations, 137 different sequence alterations of ATM were identified. Seven of these were mutations presumed to cause ataxia telangiectasia based on their effect on the ATM protein, including five that caused a protein truncation and two missense mutations in the catalytic kinase domain of the highly conserved COOH terminus of the protein. The seven mutations were found in 10 families (3.7%). In addition, one missense variant, L1420F, was observed in 13 HBOC families (4.8%) but was not observed in any of the 122 healthy volunteers with no history of breast cancer. In addition, the variant segregated with breast cancer in some of the families, suggesting that it may be pathogenic for breast cancer. Sixty-two additional variants of potential significance were observed in 65 HBOC families, but not in healthy controls. These variants included 24 sequence alterations with possible effects on splicing or protein-protein interactions. This study indicates that there is a significant prevalence of ATM mutations in breast and ovarian cancer families and adds to a growing body of evidence that ATM mutations confer increased susceptibility to breast cancer.