Clinical Cancer Research, Vol 3, Issue 6 1009-1016, Copyright © 1997 by American Association for Cancer Research

ARTICLES

Genetic alteration mapping on chromosome 7 in primary breast cancer

I Bieche, A Khodja, K Driouch and R Lidereau
Laboratoire d'Oncogenetique, Centre Rene Huguenin, 35 rue Dailly, F-92211 St-Cloud, France.

Alterations of chromosome 7 are among the most frequent cytogenetic abnormalities found in human breast carcinoma. We examined genetic changes on chromosome 7 in 113 primary human breast tumors, using both microsatellite and restriction fragment length polymorphism/variable number of tandem repeats polymorphism markers mapping to the long arm (15 markers) 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 chromosome 7 and in 41 (36%) tumors on the short arm. Genetic changes of one arm were significantly associated with alterations of the other arm. The 50 7q-altered tumor DNAs exclusively showed a loss of heterozygosity (LOH), 23 (46%) at all informative loci tested on 7q and 27 (54%) at some loci (interstitial and/or telomeric deletions on 7q). The pattern of LOH of these 27 tumors enabled us to identify 3 distinct consensus regions of deletions on 7q, only 1 of which (7q31 region) has already 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. Fourteen tumor DNAs showed an allelic gain, and 18 tumor DNAs showed a LOH at each locus on the short arm. The other 9 7p-altered tumors showing partial random alterations of chromosome 7p revealed no common altered regions. This is the first report of an association between alterations of DNA sequences on chromosome 7p and breast cancer. The results suggest that tumor suppressor genes are present on the long arm of chromosome 7 and are associated with breast tumorigenesis. Moreover, the frequent loss or gain of a whole copy of chromosome 7p suggests the involvement of a gene dosage effect of this chromosomal arm in the pathogenesis of breast cancer.

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