Inactivation of tumor suppressor genes, p53 and Rb1, in plasma cell dyscrasias.
The role of loss or inactivation of the retinoblastoma (Rb1) and p53 tumor suppressor genes in the pathogenesis of various human malignancies has been well established, yet little is known regarding plasma cell dyscrasias. In the present study, the loss of Rb1 protein expression, and the presence of Rb1 gene rearrangements as well as the presence of p53 somatic mutations (exons 5 through 9) were investigated in a panel of plasma cell dyscrasias, including 15 monoclonal gammopathies of undetermined significance (MGUS), 63 multiple myelomas (MM), and 18 plasma cell leukemias (PCL). In the same panel of cases, we established the frequency of ras oncogene mutations, the main genetic lesion associated with MM. We report that loss of Rb1 protein and p53 mutations are detectable in 34.7 and 9.8% of MM and PCL primary cases; no lesion was found in MGUS. In advanced stage MM, and PCL cases, Rb1 and p53 inactivation, as well as ras mutations were detected. Our findings show that Rb1 and p53 inactivation are associated with aggressive plasma cell dyscrasias, suggesting a role for these lesions in tumor progression rather than initiation.
Corradini
P
P
Department of Pathology, College of Physicians and Surgeons, Columbia University, NY.
Inghirami
G
G
Astolfi
M
M
Ladetto
M
M
Voena
C
C
Ballerini
P
P
Gu
W
W
Nilsson
K
K
Knowles
D M
DM
Boccadoro
M
M
D001483:Base Sequence; D015139:Blotting, Southern; D005786:Gene Expression Regulation; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D016161:Genes, Retinoblastoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000235:genetics; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics; D009154:Mutation; D010265:Paraproteinemias / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis