title: Classify hyperdiploidy status of multiple myeloma patients using gene expression profiles.
abstract: Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently harbors alterations in DNA and chromosome copy numbers, and can be divided into two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma (NHMM). The two subtypes have different survival prognosis, possibly due to different but converging paths to oncogenesis. Existing methods for identifying the two subtypes are fluorescence in situ hybridization (FISH) and copy number microarrays, with increased cost and sample requirements. We hypothesize that chromosome alterations have their imprint in gene expression through dosage effect. Using five MM expression datasets that have HMM status measured by FISH and copy number microarrays, we have developed and validated a K-nearest-neighbor method to classify MM into HMM and NHMM based on gene expression profiles. Classification accuracy for test datasets ranges from 0.83 to 0.88. This classification will enable researchers to study differences and commonalities of the two MM subtypes in disease biology and prognosis using expression datasets without need for additional subtype measurements. Our study also supports the advantages of using cancer specific characteristics in feature design and pooling multiple rounds of classification results to improve accuracy. We provide R source code and processed datasets at www.ChengLiLab.org/software.
authors.affiliation: Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Yingxiang
authors.initials: Y
authors.lastname: Li
authors.forename: Xujun
authors.initials: X
authors.lastname: Wang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zheng
authors.forename: Chengyang
authors.initials: C
authors.lastname: Wang
authors.forename: Stéphane
authors.initials: S
authors.lastname: Minvielle
authors.forename: Florence
authors.initials: F
authors.lastname: Magrangeas
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Parantu K
authors.initials: PK
authors.lastname: Shah
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
mesh_terms: D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011123:Polyploidy; D015203:Reproducibility of Results; D014314:Trisomy
references.citation: Annu Rev Pathol. 2011;6:249-74
references.pmid: 21261519
references.citation: J Clin Oncol. 2009 Sep 20;27(27):4585-90
references.pmid: 19687334
references.citation: Br J Haematol. 2002 Sep;118(4):1041-7
references.pmid: 12199783
references.citation: Leukemia. 1998 Jun;12(6):960-9
references.pmid: 9639426
references.citation: Genes Chromosomes Cancer. 2006 Dec;45(12):1111-20
references.pmid: 16955468
references.citation: Genome Biol. 2004;5(10):R80
references.pmid: 15461798
references.citation: Lancet. 2009 Jul 25;374(9686):324-39
references.pmid: 19541364
references.citation: Nat Genet. 2006 Sep;38(9):1043-8
references.pmid: 16921376
references.citation: Nature. 2004 Nov 18;432(7015):338-41
references.pmid: 15549096
references.citation: Blood. 2012 May 24;119(21):e148-50
references.pmid: 22496154
references.citation: Br J Haematol. 2007 Feb;136(4):565-73
references.pmid: 17367409
references.citation: Blood. 2011 Jul 21;118(3):675-8
references.pmid: 21628407
references.citation: Leukemia. 2003 Feb;17(2):427-36
references.pmid: 12592343
references.citation: Nat Rev Cancer. 2007 Aug;7(8):585-98
references.pmid: 17646864
references.citation: Am J Hematol. 2007 Dec;82(12):1080-7
references.pmid: 17654686
references.citation: Bioinformatics. 2004 Feb 12;20(3):307-15
references.pmid: 14960456
references.citation: Blood. 2010 Oct 7;116(14):2543-53
references.pmid: 20574050
references.citation: Cancer Res. 2007 Apr 1;67(7):2982-9
references.pmid: 17409404
references.citation: Genes Chromosomes Cancer. 2007 Jan;46(1):75-86
references.pmid: 17044051
references.citation: Nucleic Acids Res. 2003 Feb 15;31(4):e15
references.pmid: 12582260