TY - JOUR
T1 - High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients
AU - Carrasco, Daniel R.
AU - Tonon, Giovanni
AU - Huang, Yongsheng
AU - Zhang, Yunyu
AU - Sinha, Raktim
AU - Feng, Bin
AU - Stewart, James P.
AU - Zhan, Fenghuang
AU - Khatry, Deepak
AU - Protopopova, Marina
AU - Protopopov, Alexei
AU - Sukhdeo, Kumar
AU - Hanamura, Ichiro
AU - Stephens, Owen
AU - Barlogie, Bart
AU - Anderson, Kenneth C.
AU - Chin, Lynda
AU - Shaughnessy, John D.
AU - Brennan, Cameron
AU - DePinho, Ronald A.
N1 - Funding Information:
We wish to thank John Quackenbush for critical reading and advice. This work was supported by The Fund to Cure Myeloma; NCI grants RO1 CA93947, RO1 CA099041, and P50 CA93683 to L.C.; and the Robert A. and Renee E. Belfer Foundation Institute for Innovative Science at the DFCI. R.A.D. is an ACS Research Professor and Ellison Medical Foundation Senior Scholar. D.R.C. is a supported by a Mentored Clinician Scientist Award (K08AG0103) and is a Sidney Kimmel Foundation Scholar. G.T. is supported by a SPORE MM Career Development Award. Additional support was provided by grants CA84313 (R.A.D.), CA55819 (J.D.S. and B.B.), CA55819 (J.D.S.), PO1 CA78373 (K.C.A.), and SPORE P50 CA100707 (K.C.A.).
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=33645769276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645769276&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2006.03.019
DO - 10.1016/j.ccr.2006.03.019
M3 - Article
C2 - 16616336
AN - SCOPUS:33645769276
SN - 1535-6108
VL - 9
SP - 313
EP - 325
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -