High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients.
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.
Carrasco
Daniel R
DR
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Tonon
Giovanni
G
Huang
Yongsheng
Y
Zhang
Yunyu
Y
Sinha
Raktim
R
Feng
Bin
B
Stewart
James P
JP
Zhan
Fenghuang
F
Khatry
Deepak
D
Protopopova
Marina
M
Protopopov
Alexei
A
Sukhdeo
Kumar
K
Hanamura
Ichiro
I
Stephens
Owen
O
Barlogie
Bart
B
Anderson
Kenneth C
KC
Chin
Lynda
L
Shaughnessy
John D
JD
Brennan
Cameron
C
Depinho
Ronald A
RA
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