title: Genomic imbalance defines three prognostic groups for risk stratification of patients with chronic lymphocytic leukemia.
abstract: Array comparative genomic hybridization (aCGH) has yet to be fully leveraged in a prognostic setting in chronic lymphocytic leukemia (CLL). Genomic imbalance was assessed in 288 CLL specimens using a targeted array. Based on 20 aberrations in a hierarchical manner, all 228 treatment-naive specimens were classified into a group with poor outcome (20.6%) exhibiting at least one aberration that was univariately associated with adverse outcome (gain: 2p, 3q, 8q, 17q, loss: 7q, 8p, 11q, 17p, 18p), good outcome (32.5%) showing 13q14 loss without any of the other 10 aberrations (gain: 1p, 7p, 12, 18p, 18q, 19, loss: 4p, 5p, 6q, 7p) or intermediate outcome (remainder). The three groups were significantly separated with respect to time to first treatment and overall survival (p < 0.001), and validation of the stratification scheme was performed in two independent datasets. Gain of 3q and 8q, and 17p loss were determined to be independent unfavorable prognostic biomarkers. TP53, NOTCH1 and SF3B1 mutations correlated with the presence of one poor outcome aCGH marker, at a considerably higher frequency than when only considering poor risk aberrations routinely detected by fluorescence in situ hybridization (FISH). These data support genomic imbalance evaluation in CLL by aCGH to assist in risk stratification.
authors.affiliation: Cancer Genetics, Inc. , Rutherford, NJ , USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Houldsworth
authors.forename: Asha
authors.initials: A
authors.lastname: Guttapalli
authors.forename: Venkata
authors.initials: V
authors.lastname: Thodima
authors.forename: Xiao Jie
authors.initials: XJ
authors.lastname: Yan
authors.forename: Geetu
authors.initials: G
authors.lastname: Mendiratta
authors.forename: Tania
authors.initials: T
authors.lastname: Zielonka
authors.forename: Gouri
authors.initials: G
authors.lastname: Nanjangud
authors.forename: Weiyi
authors.initials: W
authors.lastname: Chen
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Anthony
authors.initials: A
authors.lastname: Mato
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.forename: Kanti
authors.initials: K
authors.lastname: Rai
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
authors.forename: R S K
authors.initials: RS
authors.lastname: Chaganti
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D055028:Comparative Genomic Hybridization; D066264:Datasets as Topic; D005260:Female; D023281:Genomics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains
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