Evaluation of Fanconi Anemia genes in familial breast cancer predisposition.
Evaluation of Fanconi Anemia genes in familial breast cancer predisposition.
复制标题
范可尼贫血基因在家族性乳腺癌易感性中的评估。
作者：
S. Seal;R. Barfoot;H. Jayatilake;Paula L. Smith;A. Renwick;L. Bascombe;L. McGuffog;D. Evans;D. Eccles;D. Easton;M. Stratton;N. Rahman
Fanconi贫血(FA)是一种常染色体隐性遗传综合征，以先天性异常、进行性骨髓衰竭和癌症易感性为特征。FA有八个已知的互补组，由至少七个基因的突变引起。最近发现双等位基因BRCA2突变导致FA-D1。BRCA2基因的单等位(杂合)突变会增加患乳腺癌的风险，是家族性乳腺癌的主要原因。为了研究其他FA基因的杂合变异是否是高外显性乳腺癌易感等位基因，我们从88个BRCA1/2阴性家系的胚系DNA中筛选出FANCA、FANCC、FANCD2、FANCA、FANCF和FANCG的突变。共鉴定出69个序列变异体，其中25个为外显子。所有外显子变异都没有导致翻译框架移位或无意义密码子，14个外显子变异是先前记录的多态。在剩下的11个外显子变异中，2个导致了同义变化，7个出现在对照中。只有两个保守的错义变异，一个在FANCA中，一个在FANCE中，分别在一个家庭中被发现，并且在300名对照中没有出现。结果表明，除BRCA2外，FA基因突变不太可能是高穿透性乳腺癌易感性的常见原因。
Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure, and susceptibility to cancer. FA has eight known complementation groups and is caused by mutations in at least seven genes. Biallelic BRCA2 mutations were shown recently to cause FA-D1. Monoallelic (heterozygous) BRCA2 mutations confer a high risk of breast cancer and are a major cause of familial breast cancer. To investigate whether heterozygous variants in other FA genes are high penetrance breast cancer susceptibility alleles, we screened germ-line DNA from 88 BRCA1/2-negative families, each with at least three cases of breast cancer, for mutations in FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG. Sixty-nine sequence variants were identified of which 25 were exonic. None of the exonic variants resulted in translational frameshifts or nonsense codons and 14 were polymorphisms documented previously. Of the remaining 11 exonic variants, 2 resulted in synonymous changes, and 7 were present in controls. Only 2 conservative missense variants, 1 in FANCA and 1 in FANCE, were each found in a single family and were not present in 300 controls. The results indicate that FA gene mutations, other than in BRCA2, are unlikely to be a frequent cause of highly penetrant breast cancer predisposition.
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影响因子：
11.2
作者：
M. Moynahan;Tracy Y. Cui;M. Jasin
通讯作者：
M. Moynahan;Tracy Y. Cui;M. Jasin
影响因子：
16
作者：
Garcia-Higuera, I;Taniguchi, T;D'Andrea, AD
通讯作者：
D'Andrea, AD
影响因子：
9.8
作者：
Ford, D;Easton, DF;Vasen, H
通讯作者：
Vasen, H
范可尼贫血杂合子癌症易感性的重新评估。
DOI：
--
发表时间：
1980
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Swift,M;Caldwell,RJ;Chase,C
通讯作者：
Chase,C