p16(INK4a) and p15(INK4b) gene methylations in plasma cells from monoclonal gammopathy of undetermined significance.
p15(INK4b) and p16(INK4a) proteins are cell cycle regulators involved in the inhibition of G1 phase progression. High frequency of methylation of both genes has been reported in multiple myeloma (MM), but it remains to be determined how and when these alterations contribute to tumorigenesis. Monoclonal gammopathy of undetermined significance (MGUS) represents an early disease stage in a fraction of MMs. Plasma cells from 33 patients with MGUS and 33 patients with MM were isolated and analyzed for p15(INK4b) and p16(INK4a) methylation by methylation-specific polymerase chain reaction. Selective methylation was found in 19% for p16(INK4a), 36% for p15(INK4b), and 6.5% for both genes in MGUS, and frequencies were similar in MM suggesting that methylation of these genes is an early event, not associated with transition from MGUS to MM. p15(INK4b) and p16(INK4a) gene methylation might contribute to immortalization of plasma cells rather than malignant transformation in the natural history of MM.
Guillerm
G
G
Unité Institut National de la Santé et de la Recherche Médicale 524, Institut de Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille, France.
Gyan
E
E
Wolowiec
D
D
Facon
T
T
Avet-Loiseau
H
H
Kuliczkowski
K
K
Bauters
F
F
Fenaux
P
P
Quesnel
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D010265:Paraproteinemias / Q000235:genetics* / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins