title: High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients.
abstract: To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Carrasco
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tonon
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Huang
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Raktim
authors.initials: R
authors.lastname: Sinha
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: James P
authors.initials: JP
authors.lastname: Stewart
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Deepak
authors.initials: D
authors.lastname: Khatry
authors.forename: Marina
authors.initials: M
authors.lastname: Protopopova
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.forename: Kumar
authors.initials: K
authors.lastname: Sukhdeo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hanamura
authors.forename: Owen
authors.initials: O
authors.lastname: Stephens
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Cameron
authors.initials: C
authors.lastname: Brennan
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Depinho
mesh_terms: D002877:Chromosomes, Human / Q000145:classification / Q000235:genetics; D004171:Diploidy; D018572:Disease-Free Survival; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D009101:Multiple Myeloma / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis