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Frequent hypermethylation of p16 and p15 genes in multiple myeloma
MH Ng, YF Chung, KW Lo, NW Wickham, JC Lee and DP Huang
Department of Anatomical & Cellular Pathology, The Chinese University
of Hong Kong, Shatin.
Both p16 and p15, encoded by the genes located on chromosome 9p21, are
inhibitors of cyclin-dependent kinases (CDK4/6) and the upstream regulators
of Rb function. In hematopoietic malignancies, deletion of p16/p15 locus
has been shown to be highly specific to lymphoid, and more particularly
from B-lineage malignancies except multiple myeloma (MM). To investigate
whether these genes are inactivated by deletions, mutations, and
hypermethylation of the 5' CpG islands, we examined 12 MM patients by
Southern hybridization and polymerase chain reaction- single-strand
conformation polymorphism (PCR-SSCP) analysis. No deletions nor mutations
of the p16 and p15 genes were found. However, hypermethylation was observed
in 75% for p16 and 67% for p15 in our group of MM patients. Such high
frequencies of involvement of these genes in MM make them hitherto the most
common genetic abnormalities in this disease. Concomitant hypermethylation,
uncommon thus far in the literature of the study of these genes, is a
rather common phenomenon, occurring in 67% of our patient group. Moreover,
hypermethylation of p16/p15 was associated with blastic disease and
concomitant hypermethylation of both genes may be pathogenetically related
to plasmacytoma development. These results indicate that these genes are
important in MM pathogenesis. Here we report, for the first time in the
literature, the high incidences of p16 and p15 alterations in MM, not by
homozygous deletions or mutations, but solely by hypermethylation of the 5'
CpG islands, which may be a specific mechanism in this disease.
Volume 89,
Issue 7,
pp. 2500-2506,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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