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Open Access Green as soon as Postprint is submitted to ZB.
Different mechanisms of cyclin D1 overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analysis of mRNA levels.
Blood 104, 1120-1126 (2004)
The t(11;14)(q13;q32) is the most com-
mon translocation in multiple myeloma
(MM), resulting in up-regulation of cyclin
D1. We used a segregation fluorescence
in situ hybridization (FISH) assay to de-
tect t(11;14) breakpoints in primary MM
cases and real-time reverse transcriptase–
polymerase chain reaction (RT-PCR) to
quantify cyclin D1 and MYEOV (myeloma
overexpressed) expression, another puta-
tive oncogene located on chromosome
11q13. High levels of cyclin D1 mRNA
(cyclin D1/TBP [TATA box
binding pro-
tein] ratio
>
95) were found exclusively in
the presence of a t(11;14) translocation
(11/48 cases;
P
<
.00001). In addition, a
subgroup of MM cases (15/48) with inter-
mediate to low cyclin D1 mRNA (cyclin
D1/TBP ratio between 2.3 and 20) was
identified. FISH analysis ruled out a t(11;
14) translocation and 11q13 amplification
in these cases; however, in 13 of 15
patients a chromosome 11 polysomy was
demonstrated (
P
<
.0001). These results
indicate an effect of gene dosage as an
alternative mechanism of cyclin D1 de-
regulation in MM. The absence of chromo-
some 11 abnormalities in 2 of 15 patients
with intermediate cyclin D1 expression
supports that there are presumably other
mechanism(s) of cyclin D1 deregulation
in MM patients. Our data indicate that
deregulation of MYEOV is not favored in
MM and further strengthens the role of
cyclin D1 overexpression in lymphoid ma-
lignancies with a t(11;14)(q13;q32) trans-
location.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 104,
Issue: 4,
Pages: 1120-1126
Publisher
American Society of Hematology
Reviewing status
Peer reviewed
Institute(s)
Institute of Pathology (PATH)