title: A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
abstract: 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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Chung
authors.forename: George
authors.initials: G
authors.lastname: Mulligan
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D043171:Chromosomal Instability; D002986:Clinical Trials as Topic; D055028:Comparative Genomic Hybridization; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000627:therapeutic use; D012306:Risk; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib