Detailed deletion mapping of chromosome segment 17q12-21 in sporadic breast tumours.

Linkage studies have indicated that a gene on chromosome arm 17q, designated BRCAI, confers susceptibility to familial breast and ovarian cancer. To investigate the possible involvement of the BRCAI gene in sporadic breast cancer we have analysed loss of heterozygosity (LOH) in a panel of 100 sporadic primary breast tumours using 10 PCR‐based polymorphic markers from 17q12–21. Allele losses were detected in 40 of 100 tumours informative for at least one of the markers analysed. Of these 40 deleted tumours, 27 showed partial or interstitial loss on 17q. The pattern of LOH in the tumours with partial or interstitial LOH revealed three putative distinct deleted regions on 17q12–21. The first lies on the proximal long arm between D17S250 and THRAI; the second one lies between D17S776 and D17S579, the region containing the BRCAI gene; and the third is telomeric to D17S733. The most frequently deleted region overlaps with the minimal region containing the BRCAI gene, suggesting that this gene might also be associated with the development or progression of a proportion of sporadic breast tumours.

[1]  D. Easton,et al.  Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. , 1993, American journal of human genetics.

[2]  R. Lidereau,et al.  Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Conway,et al.  Familial breast-ovarian cancer locus on chromosome 17q12-q23 , 1991, The Lancet.

[4]  J. Weber,et al.  Dinucleotide repeat polymorphism at the D15S87 locus. , 1990, Nucleic acids research.

[5]  P. Devilee,et al.  Allele loss patterns on chromosome 17q in 109 breast carcinomas indicate at least two distinct target regions. , 1993, Oncogene.

[6]  D. Easton,et al.  Allele losses in the region 17q12–21 in familial breast and ovarian cancer involve the wild–type chromosome , 1992, Nature Genetics.

[7]  P L Pearson,et al.  Allelotype of human breast carcinoma: a second major site for loss of heterozygosity is on chromosome 6q. , 1991, Oncogene.

[8]  M. Skolnick,et al.  A large kindred with 17q-linked breast and ovarian cancer: genetic, phenotypic, and genealogical analysis. , 1994, Journal of the National Cancer Institute.

[9]  P. Tonin,et al.  Genetic mapping of the breast-ovarian cancer syndrome to a small interval on chromosome 17q12-21: exclusion of candidate genes EDH17B2 and RARA. , 1993, Human molecular genetics.

[10]  W. McGuire,et al.  Follow-up study of HER-2/neu amplification in primary breast cancer. , 1991, Cancer research.

[11]  M. King,et al.  Two independent polymorphisms at the 17 beta-hydroxysteroid dehydrogenase (EDH17B) gene (17q21). , 1993, Human molecular genetics.

[12]  A. Tanigami,et al.  Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. , 1990, Cancer research.

[13]  Y. Nakamura,et al.  Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors. , 1993, Cancer research.

[14]  L. Liotta,et al.  Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. , 1989, Cancer research.

[15]  M. King,et al.  High-density genetic map of the BRCA1 region of chromosome 17q12-q21. , 1993, Genomics.

[16]  E. Fujimoto,et al.  Genetic mapping of the BRCA1 region on chromosome 17q21. , 1994, American journal of human genetics.

[17]  J. Barrett,et al.  Dinucleotide repeat polymorphism in the THRA1 gene. , 1992, Human molecular genetics.

[18]  G. Gyapay,et al.  A second-generation linkage map of the human genome , 1992, Nature.

[19]  L. Liotta,et al.  Somatic allelic deletion of nm23 in human cancer. , 1991, Cancer research.

[20]  J. Barrett,et al.  Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite length polymorphisms. , 1992, Cancer research.

[21]  M. King,et al.  Linkage of early-onset familial breast cancer to chromosome 17q21. , 1990, Science.

[22]  J E Talmadge,et al.  Evidence for a novel gene associated with low tumor metastatic potential. , 1988, Journal of the National Cancer Institute.

[23]  J. Nesland,et al.  Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas , 1992, Genes, chromosomes & cancer.

[24]  J. Weber,et al.  Closing in on a breast cancer gene on chromosome 17q. , 1992, American journal of human genetics.

[25]  H. Lynch,et al.  Epidemiology and Risk Factors , 1989, Clinical obstetrics and gynecology.

[26]  D. Kelsell,et al.  Genetic analysis of the BRCA1 region in a large breast/ovarian family: refinement of the minimal region containing BRCA1. , 1993, Human molecular genetics.