Frequent occurrence of CCND1 deregulation in patients with early stages of plasma cell dyscrasia.
Chromosomal translocations involving the immunoglobulin heavy chain gene (IgH) and nonrandom protooncogene loci are the hallmark of genetic alterations found not only in multiple myeloma (MM), but also in premalignant stages of MM, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). We studied the frequency of IgH (14q32) rearrangements and their partner chromosomes in 16 Japanese patients with MGUS (13 cases), and SMM (3 cases) by means of interphase double-color fluorescence in situ hybridization (DCFISH) applied to purified plasma cells and using CD138-bead selection. IgH rearrangement was recognized in nine of the patients (56.3%). Protooncogene loci juxtaposed to IgH were identified in seven cases including CCND1 (11q13) in six cases and FGFR3 (4p16) in one. Four out of the six t(11;14)-positive cases showed nuclear staining of the cyclin D1 protein, whereas none of the seven t(11;14)-negative cases did. Moreover, neither MUM1(6p25)-IgH nor MAFB(20q11)-IgH fusion signals were observed. This suggests to us that cyclin D1 deregulation due to the presence of t(11;14) is involved in the early development of plasma cell neoplasms, and that this event alone is not enough for the development of symptomatic myeloma.
Miura
Kazuhisa
K
Department of Internal Medicine & Molecular Science, Nagoya City University Graduate School of Medical Science, Mizuho-ku, Nagoya 467-8601, Japan.
Iida
Shinsuke
S
Hanamura
Ichiro
I
Kato
Miyuki
M
Banno
Shogo
S
Ishida
Takashi
T
Kusumoto
Shigeru
S
Takeuchi
Genji
G
Miwa
Hiroshi
H
Nitta
Masakazu
M
Inagaki
Hiroshi
H
Eimoto
Tadaaki
T
Nomura
Kenichi
K
Taniwaki
Masafumi
M
Ueda
Ryuzo
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010265:Paraproteinemias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D019938:Cyclin D1