BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants

被引:228
作者
Elstrodt, F
Hollestelle, A
Nagel, JHA
Gorin, M
Wasielewski, M
van den Ouweland, A
Merajver, SD
Ethier, SP
Schutte, M
机构
[1] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Med Oncol, NL-3000 DR Rotterdam, Netherlands
[2] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands
[3] Univ Michigan, Ctr Canc, Dept Internal Med, Ann Arbor, MI 48109 USA
[4] Barbara Ann Karmanos Canc Inst, Detroit, MI USA
关键词
D O I
10.1158/0008-5472.CAN-05-2853
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Germ line mutations of the BRCA1 gene confer a high risk of breast cancer and ovarian cancer to female mutation carriers. The BRCA1 protein is involved in the regulation of DNA repair. How specific tumor-associatcd mutations affect the molecular function of BRCA1, however, awaits further elucidation. Cell lines that harbor BRCA1 gene mutations are invaluable tools for such functional studies. Up to now, the HCC1937 cell line was the only human breast cancer cell line with an identified BRCA1 initiation. In this study, we identified three other BRCA1 mutants from among 41 human breast cancer cell lines by sequencing of the complete coding sequence of BRCA1. Cell line MDA-MB-436 had the 5396 + 1G>A mutation in the splice donor site of exon 20. Cell line SUM149PT carried the 2288delT mutation and SUM1315M02 carried the 185delAG mutation. All three mutations were accompanied by loss of the other BRCA1 allele. The 185delAG and 5396 + 1G>A mutations are both classified as pathogenic mutations. In contrast with wildtype cell lines, none of the BRCA1 mutants expressed nuclear BRCA1 proteins as detected with Ab-1 and Ab-2 anti-BRCA1 monoclonal antibodies. These three new human BRCA1 mutant cell lines thus seem to be representative breast cancer models that could aid in further unraveling of the function of BRCA1.
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页码:41 / 45
页数:5
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