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Human breast cancer: genetic alterations in the MET gene region
L Tougas1, F Halwani, G Tremblay
1Department of Pathology, McGill University, Royal Victoria Hospital, Montreal, Que.
Objective:
to test whether the MET gene at chromosome 7q31, which encodes a receptor protein (tyrosine kinase) related to normal histological differentiation, undergoes structural changes in breast cancer. A previous study reported somatic alterations detected as loss of heterozygosity (LOH) at this locus in breast cancer.
Design:
Analysis of DNA from tumours and matched normal tissue by Southern blot hybridization with the metH probe; the tumours were also analysed for estrogen and progesterone receptors, ploidy and S phase, and protein expression of the MET and c-erbB-2 protooncogenes.
Participants:
Eighty-two patients with breast cancer.
Results:
Fifty-three percent of the patients were informative for polymorphism with the metH marker. Somatic alterations of MET, consisting of LOH, were demonstrated in 22% of women who were informative and had breast cancer. No correlation was found between LOH of MET and conventional prognostic factors, or status for c-erbB-2 proto-oncogene expression. Estrogen-receptor status correlated with progesterone-receptor status, and S phase correlated with ploidy and size of the tumour.
Conclusions:
Somatic alterations of MET, detected as LOH with the metH probe, occur in 22% of informative patients. These alterations do not correlate with the prognostic factors established when the mastectomy is performed. It remains to be determined whether the patients' overall survival and disease-free survival rates are correlated with genetic alteration of MET.