GENETIC ALTERATION MAPPING ON CHROMOSOME-7 IN PRIMARY BREAST-CANCER

Alterations of chromosome 7 are among the most frequent cytogenetic ab normalities found in human breast carcinoma, We examined genetic chang es on chromosome 7 in 113 primary human breast tumors, using both micr osatellite and restriction fragment length polymorphism/variable numbe r of tandem repeats polymorphism markers mapping to the long arm (15 m arkers) and the short arm (8 markers), Allelic imbalance at 1 or more loci was observed in 50 (44%) of 113 tumors on the long arm of chromos ome 7 and in 41 (36%) tumors on the short arm, Genetic changes of one arm were significantly associated with alterations of the other arm, T he 50 7q-altered tumor DNAs exclusively showed a loss of heterozygosit y (LOH), 23 (46%) at all informative loci tested on 7q and 27 (54%) at some loci (interstitial and/or telomeric deletions on 7q). The patter n of LOH of these 27 tumors enabled us to identify 3 distinct consensu s regions of deletions on 7q, only 1 of which (7q31 region) has alread y been described in breast cancer. Among the 41 7p-altered tumor DNAs, 32 had a gain and/or loss of the entire short arm of chromosome 7. Fo urteen tumor DNAs showed an allelic gain, and 18 tumor DNAs showed a L OH at each locus on the short arm, The other 9 7p-altered tumors showi ng partial random alterations of chromosome 7p revealed no common alte red regions, This is the first report of an association between altera tions of DNA sequences on chromosome 7p and breast cancer, The results suggest that tumor suppressor genes are present on the long arm of ch romosome 7 and are associated with breast tumorigenesis, Moreover, the frequent loss or gain of a whole copy of chromosome 7p suggests the i nvolvement of a gene dosage effect of this chromosomal arm in the path ogenesis of breast cancer.