TY - JOUR
T1 - A Novel Measure of Chromosome Instability Can Account for Prognostic Difference in Multiple Myeloma
AU - Chung, Tae Hoon
AU - Mulligan, George
AU - Fonseca, Rafael
AU - Chng, Wee Joo
N1 - Funding Information:
GM is an employee of Millenium: The Takeda Oncology Company. RF has received consulting fees from Medtronic, Otsuka, Celgene, Genzyme, BMS, Lilly, Millenium and AMGEN. He also has sponsored research from Cylene and Onyx. WJC has received research funding from Celgene and Roche, as well as honorarium from Novartis, Merck, Celgene, Janssen, and Bristol-Myers Squibb. However, this does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2013/6/20
Y1 - 2013/6/20
N2 - Multiple myeloma (MM) is characterized by complex genetic abnormalities whose complexity signifies varying degree of chromosomal instability (CIN). In this study, we introduced a novel CIN measure, chromosome instability genome event count (CINGEC), which considered both copy number aberrations and interstitial breakpoints from high-resolution genome-wide assays. When assessed in two aCGH MM datasets, higher CINGEC was associated with poor survival. We then derived a CINGEC-associated gene expression profile (GEP) signature, CINGECS, using a dataset that has both aCGH and GEP. Genes in CINGECS were mainly involved in DNA damage responses besides in aneuploidy and other generic oncogenic processes contrary to other CIN associated GEP signatures. Finally, we confirmed its survival association in three GEP datasets that encompassed newly diagnosed patients treated with transplant-based protocol with or without novel agents for induction as well as relapsed patients treated with bortezomib. Furthermore, CINGECS was independent of many GEP-based prognostic signatures. In conclusion, our novel CIN measure has definite biological and clinical significance in myeloma.
AB - Multiple myeloma (MM) is characterized by complex genetic abnormalities whose complexity signifies varying degree of chromosomal instability (CIN). In this study, we introduced a novel CIN measure, chromosome instability genome event count (CINGEC), which considered both copy number aberrations and interstitial breakpoints from high-resolution genome-wide assays. When assessed in two aCGH MM datasets, higher CINGEC was associated with poor survival. We then derived a CINGEC-associated gene expression profile (GEP) signature, CINGECS, using a dataset that has both aCGH and GEP. Genes in CINGECS were mainly involved in DNA damage responses besides in aneuploidy and other generic oncogenic processes contrary to other CIN associated GEP signatures. Finally, we confirmed its survival association in three GEP datasets that encompassed newly diagnosed patients treated with transplant-based protocol with or without novel agents for induction as well as relapsed patients treated with bortezomib. Furthermore, CINGECS was independent of many GEP-based prognostic signatures. In conclusion, our novel CIN measure has definite biological and clinical significance in myeloma.
UR - http://www.scopus.com/inward/record.url?scp=84879266916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879266916&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0066361
DO - 10.1371/journal.pone.0066361
M3 - Article
C2 - 23840451
AN - SCOPUS:84879266916
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 6
M1 - e66361
ER -