Tumor suppressor genes
Springer Online Journal Archives 1860-2000
Conclusions Changes in proto-oncogenes and tumor-suppressor genes at the molecular level are associated with the development and progression of testicular GCTs (Fig. 3). Investigations at this level, however, are only in their initial stages, and therefore the overall genetic changes which lead to the development of a metastasizing tumor are not known. Investigations show however, that undifferentiated GCTs (seminoma, embryonal carcinoma, chorionepithelioma) display molecular changes that are different from those of differentiated GCTs (teratocarcinoma, mixed tumors). In undifferentiated GCTs the following changes have been demonstrated: an increased expression of the proto-oncogenes c-kit, N-myc, c-myc, and c-mos; mutations in N-ras; missing expression in the RB tumor-suppressor gene; and a general hypomethylation of the DNA. These events possibly lead to a blockade of the differentiation process, and these GCTs may therefore correspond to an earlier stage of embryogenesis. These changes, on the other hand, do not occur in GCTs with differentiated tissue parts. The conspicuous expression of the c-erbB1 and c-erbB2 proto-oncogenes and also that of the RB tumor-suppressor gene is clearly associated in these tumors with differentiation. Important events in the formation or progression of teratocarcinoma and of the partly differentiated nonseminoma are, moreover, a generally lower number of copies of chromosome 15, a possible LOH at the nm23 locus, and hypermethylation, which may result in a switching off of particular genes. How the above molecular changes actually provide a clinically relevant supplement to the traditional classification of GCTs must be demonstrated by further investigations.
Type of Medium: