title: Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma.
abstract: A specific role for increased level of expression of CKS1B, as a consequence of chromosome 1q21 copy number gain, has been postulated as both pathogenic, as well as a powerful clinical prognostic factor in multiple myeloma (MM). The purpose of this study is to determine the clinical associations and prognostic impact of copy number gain at chromosome 1q21 (with a bacteria artificial chromosome clone containing CKS1B) and CKS1B gene level of expression in MM. We studied the chromosome region 1q21 for copy number change in a cohort of myeloma patients treated by high-dose therapy with stem-cell rescue (HDT) (n = 159). A separate cohort of patients, treated by HDT was studied for CKS1B messenger RNA expression by gene expression profiling (n = 67). 1q21 gain was then correlated with clinical parameters and survival. Gain of 1q21 copy number was detected in about a third of MM and was associated with more proliferative disease and poor-risk cytogenetic categories such as t(4;14), and chromosome 13 deletion. Both 1q21 gain and increase gene expression level were significantly associated with reduced survival. However, neither is an independent prognostic marker in MM on multivariate Cox proportional hazard analysis.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic Comprehensive Cancer Center, Scottsdale, AZ 85259, USA. fonseca.rafael@mayo.edu
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
authors.forename: S A
authors.initials: SA
authors.lastname: Van Wier
authors.forename: W J
authors.initials: WJ
authors.lastname: Chng
authors.forename: R
authors.initials: R
authors.lastname: Ketterling
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: P L
authors.initials: PL
authors.lastname: Bergsagel
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: P R
authors.initials: PR
authors.lastname: Greipp
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
authors.forename: T
authors.initials: T
authors.lastname: Price-Troska
authors.forename: K J
authors.initials: KJ
authors.lastname: Henderson
authors.forename: G J
authors.initials: GJ
authors.lastname: Ahmann
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002878:Chromosomes, Human, Pair 1; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C093090:CKS1B protein, human; D002352:Carrier Proteins; D012333:RNA, Messenger; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases