Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia, Cowden disease and BRCA1 gene regions

• Published in: Oncogene Vol. 14; no. 3; pp. 339 - 347
• Main Authors: KERANGUEVEN, F, EISINGER, F, SOBOL, H, BIRNBAUM, D, NOGUCHI, T, ALLIONE, F, WARGNIEZ, V, ENG, C, PADBERG, G, THEILLET, C, JACQUEMIER, J, LONGY, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 23-01-1997; Nature Publishing Group
• Subjects: Alleles; Ataxia; Ataxia telangiectasia; Ataxia Telangiectasia - genetics; Ataxia telangiectasia mutated protein; Biological and medical sciences; BRCA1 protein; BRCA2 protein; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Chromosome 10; Chromosome 11; Chromosome 13; Chromosome 17; Chromosome Deletion; Chromosomes; Chromosomes, Human, Pair 10 - genetics; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 17 - genetics; Disease Susceptibility; Female; Genes; Genes, BRCA1 - genetics; Genetic Markers; Gynecology. Andrology. Obstetrics; Hamartoma Syndrome, Multiple - genetics; Heterozygosity; Humans; Loss of heterozygosity; Mammary gland diseases; Medical sciences; Microsatellite Repeats - genetics; Tumor suppressor genes; Tumors; Genetic mapping; Human; Nervous system diseases; Genetic marker; Heterozygosity loss; Malignant tumor; Chromosome C10; Chromosome C11; Mammary gland diseases; Gene; Chromosome E17; Central nervous system disease; Risk factor; Predisposition; Ataxia telangiectasia; Genetics; Tumor; Mammary gland
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1200818

To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with particular emphasis on specific regions. No site of consistent LOH was identified on chromosome 10. Five regions of LOH were contained within bands q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least one marker. This region is thus a major site of deletion in breast cancer and several tumor suppressor genes seem to be involved. One of them may be the ataxia telangiectasia (ATM) gene which is located in one of the affected regions. Five regions of LOH, one of which is within the BRCA1 gene area, were recognized along chromosome 17. LOH at three of these regions were found in highly proliferative tumors. When combined with a previous study of chromosome 13 with emphasis on BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of LOH, variably affected in breast tumors and correlated with prognostic parameters.