Amplification of the c-myc and the pvt-like region in human multiple myeloma.

Genetic alterations that lead to the clonal expansion of differentiated cells in multiple myeloma have still to be elucidated. Many chromosomal aberrations have been found, but until now, none of them is typically associated with multiple myeloma. In search for genetic defects in multiple myeloma we studied the structure and expression of the c-myc oncogene and the pvt-like region because of their frequent association with other B-cell malignancies. Here we report co-amplification of the c-myc oncogene and the 5' part of the pvt-like region in two out of 26 cases of multiple myeloma. In both cases only kappa-light chains were produced. The amplification also manifested itself at the RNA level. Total RNA was analysed in one of these two cases showing abundant c-myc mRNA. In the same RNA sample we also detected a strong hybridizing band of about 7 kb, when the pSS.4 probe, representing the 5' part of the pvt-like region, was used. This band was not present in total RNA from normal bone marrow cells or bone marrow from multiple myeloma patients without the amplification of c-myc and the pvt-like region. Until now, transcripts of the pvt-like region were only found in a few human cell lines ranging in size from 1 to 11 kb. This is the first case in which a high expression of a +/- 7 kb transcript of the pvt-like region has been found in freshly obtained tumor material probably due to a pvt-amplification. The occurrence of abnormalities in the c-myc and the pvt-like region in multiple myeloma is a rare event and may be associated with the progression of this type of tumor.