Color bar coding the BRCAI gene on combed DNA:: A useful strategy for detecting large gene rearrangements

被引:48
作者
Gad, S
Aurias, A
Puget, N
Mairal, A
Schurra, C
Montagna, M
Pages, S
Caux, V
Mazoyer, S
Bensimon, A
Stoppa-Lyonnet, D
机构
[1] Inst Curie, Serv Genet Oncol, Med Sect, F-75248 Paris 05, France
[2] Inst Curie, INSERM U509 Pathol Mol Canc, Paris, France
[3] Univ Lyon 1, UMR 5641 CNRS, Int Agcy Res Canc, F-69365 Lyon, France
[4] Univ Lyon 1, UMR 5641 CNRS, Genet Lab, F-69365 Lyon, France
[5] Inst Pasteur, ADN, Biophys Lab, Paris, France
[6] Univ Padua, Interuniv Ctr Res Canc, Oncol Sect, Dept Oncol & Surg Sci, Padua, Italy
关键词
D O I
10.1002/gcc.1120
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Genetic linkage data have shown that alterations of the BRCA I gene are responsible for the majority of hereditary breast and ovarian cancers. BRCA I germline mutations, however, are found less frequently than expected. Mutation detection strategies, which are generally based on the polymerase chain reaction, therefore focus on point and small gene alterations. These approaches do not allow for the detection of large gene rearrangements, which also can be involved in BRCA/ alterations. Indeed, a few of them, spread over the entire BRCA/ gene, have been detected recently by Southern blotting or transcript analysis. We have developed an alternative strategy allowing a panoramic view of the BRCA/ gene, based on dynamic molecular combing and the design of a full four-color bar code of the BRCA/ region. The strategy was tested with the study of four large BRCA/ rearrangements previously reported. In addition, when screening a series of 10 breast and ovarian cancer families negatively tested for point mutation in BRCA 1/2, we found an unreported 17-kb BRCA/ duplication encompassing exons 3 to 8. The detection of rearrangements as small as 2 to 6 kb with respect to the normal size of the studied fragment is achieved when the BRCA/ region is divided into 10 fragments. In addition, as the BRCA/ bar code is a morphologic approach, the direct observation of complex and likely underreported rearrangements, such as inversions and insertions, becomes possible. (C) 2001 Wiley-Liss, Inc.
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页码:75 / 84
页数:10
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