Genetic variability of proto-oncogenes for breast cancer risk and prognosis

This paper summarizes the results of a study on human breast cancers performed mainly at the Centre René Huguenin in collaboration with other American and French groups, and supported in part by a Grant from the Association pour la Recherche sur le Cancer (ARC) Villejuif. During this work, the following conclusions emerged: c-myc proto-oncogene amplification is a common alteration in ductal invasive tumors, more frequently found in recurrent and metastatic tumors, suggesting a role for c-myc in tumor progression. However, in the current state of our study, it does not appear to be linked to prognosis; parts of the short arm of chromosome 11 are deleted in 20% of tumors resulting in hemizygosity for several genes (c-ha-ras, beta globin, pTH, calcitonin, catalase). These deletions seem to be linked with aggressiveness of tumors; a restriction fragment length polymorphism (RFLP) study of c-ha-ras has shown a significant association of the frequency of rare ha-ras alleles in cancer patients compared to that of normal individuals. Although this result is currently a matter of controversy, further studies must be independently repeated to be conclusive; -- another RFLP was found in c-mos proto-oncogene, which is detected only in patients with breast cancers or other types of tumors. The molecular basis for this RFLP has been elucidated. The significance of this association is unknown.