Other Molecular Aberrations Not Affecting The Ig LOCI

These include chromosomes 11q and 8 rearrangements; duplication of 1q21-31; reciprocal translocation of 1q with 15p, 16p, and 5q; p53, N-ras, and K-ras mutation; complex translocations involving three or more chromosomes, and whole arm translocations.

Aberrations of p53, the tumor suppressor gene on chromosome 17p13, have been postulated to play a role in myeloma pathogenesis, with p53 deletions found to be a predictor of poor survival.62 The p53 tumor suppressor gene is involved in the control of normal cellular proliferation, differentiation, and apoptosis, as well as DNA replication and repair. Although previous CC studies indicated a low frequency of p53 mutations and deletions in myeloma, 3-9%,62 molecular cytogenetic studies have demonstrated a much higher incidence. Monoallelic deletions of chromosome 17p involving p53 have been detected by FISH in approximately one-third of newly diagnosed myeloma patients, and were also associated with reduced survival.63 Many of these abnormalities are small interstitial deletions that are detectable only by FISH.63 The higher frequency of p53 mutations in plasma cell leukemia and relapsed disease, as compared with myeloma at diagnosis, may indicate their role as a late molecular aberration in myeloma progression.64

N-ras and K-ras mutation are rare in MGUS, indolent disease, and solitary plasmacytomas, but have been reported to occur in 10-40% of patients with active disease, and even higher in advance disease. With the more sensitive allele-specific amplification method, the frequencies are higher: 55% at diagnosis and 81% at relapse.

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