PMID- 18829482
OWN - NLM
STAT- MEDLINE
DCOM- 20081126
LR  - 20220129
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 19
DP  - 2008 Oct 1
TI  - Deletions of CDKN2C in multiple myeloma: biological and clinical implications.
PG  - 6033-41
LID - 10.1158/1078-0432.CCR-08-0347 [doi]
AB  - PURPOSE: Deletions of chromosome 1 have been described in 7% to 40% of cases of 
      myeloma with inconsistent clinical consequences. CDKN2C at 1p32.3 has been 
      identified in myeloma cell lines as the potential target of the deletion. We 
      tested the clinical impact of 1p deletion and used high-resolution techniques to 
      define the role of CDKN2C in primary patient material. EXPERIMENTAL DESIGN: We 
      analyzed 515 cases of monoclonal gammopathy of undetermined significance (MGUS), 
      smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma using 
      fluorescence in situ hybridization (FISH) for deletions of CDKN2C. In 78 myeloma 
      cases, we carried out Affymetrix single nucleotide polymorphism mapping and U133 
      Plus 2.0 expression arrays. In addition, we did mutation, methylation, and 
      Western blotting analysis. RESULTS: By FISH we identified deletion of 1p32.3 
      (CDKN2C) in 3 of 66 MGUS (4.5%), 4 of 39 SMM (10.3%), and 55 of 369 multiple 
      myeloma cases (15%). We examined the impact of copy number change at CDKN2C on 
      overall survival (OS), and found that the cases with either hemizygous or 
      homozygous deletion of CDKN2C had a worse OS compared with cases that were intact 
      at this region (22 months versus 38 months; P = 0.003). Using gene mapping we 
      identified three homozygous deletions at 1p32.3, containing CDKN2C, all of which 
      lacked expression of CDKN2C. Cases with homozygous deletions of CDKN2C were the 
      most proliferative myelomas, defined by an expression-based proliferation index, 
      consistent with its biological function as a cyclin-dependent kinase inhibitor. 
      CONCLUSIONS: Our results suggest that deletions of CDKN2C are important in the 
      progression and clinical outcome of myeloma.
FAU - Leone, Paola E
AU  - Leone PE
AD  - Section of Haemato-Oncology, The Institute of Cancer Research, 15 Cotswold Road, 
      London, United Kingdom.
FAU - Walker, Brian A
AU  - Walker BA
FAU - Jenner, Matthew W
AU  - Jenner MW
FAU - Chiecchio, Laura
AU  - Chiecchio L
FAU - Dagrada, Gianpaolo
AU  - Dagrada G
FAU - Protheroe, Rebecca K M
AU  - Protheroe RK
FAU - Johnson, David C
AU  - Johnson DC
FAU - Dickens, Nicholas J
AU  - Dickens NJ
FAU - Brito, Jose Luis
AU  - Brito JL
FAU - Else, Monica
AU  - Else M
FAU - Gonzalez, David
AU  - Gonzalez D
FAU - Ross, Fiona M
AU  - Ross FM
FAU - Chen-Kiang, Selina
AU  - Chen-Kiang S
FAU - Davies, Faith E
AU  - Davies FE
FAU - Morgan, Gareth J
AU  - Morgan GJ
LA  - eng
GR  - A6308/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (CDKN2C protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
SB  - IM
MH  - Aged
MH  - Cell Line, Tumor
MH  - Chromosome Mapping/methods
MH  - Cyclin-Dependent Kinase Inhibitor p18/*genetics
MH  - Disease Progression
MH  - *Gene Deletion
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Models, Genetic
MH  - Multiple Myeloma/diagnosis/*genetics
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC2581792
MID - UKMS2612
OID - NLM: UKMS2612
EDAT- 2008/10/03 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/04/01
CRDT- 2008/10/03 09:00
PHST- 2008/10/03 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/03 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - 14/19/6033 [pii]
AID - 10.1158/1078-0432.CCR-08-0347 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Oct 1;14(19):6033-41. doi: 10.1158/1078-0432.CCR-08-0347.