title: Biological and clinical characterization of recurrent 14q deletions in CLL and other mature B-cell neoplasms.
abstract: 14q-deletions have been repeatedly described in mature B-cell neoplasms, but not yet characterized in a larger cohort. Based on chromosome banding analysis, the present study identified 47 del(14q) cases in 3054 mature B-cell neoplasms (1·5%) (chronic lymphocytic leukaemia [CLL]: 1·9%; CLL/prolymphocytic leukaemia [PL]: 9·0%; others: 0·2%). Interphase fluorescence in situ hybridization was performed with probes for 14q22.1, 14q24.1, 14q32.33, and IGH@ (14q32.3). The del(14q) had heterogeneous size but showed a breakpoint cluster at the centromeric site in 14q24.1 (62% of cases). At the telomeric side, the most frequent breakpoint was within the IGH@ locus (14q32.3) between IGH@ 3'-flanking and IGHV (IgVH) probes (45%). In 16 cases (34%), breakpoints occurred within 14q24.1 and 14q32.3. Eighty-one percent of del(14q) cases showed 1-3 additional cytogenetic alterations (in 45%, +12), and 56% were IGHV-unmutated. In all cases (16/16) with breakpoints in 14q24.1 and 14q32.3, a B-CLL immunophenotype was found. Clinical follow-up in 32 del(14q) patients was compared to 383 CLL and CLL/PL patients without del(14q). While 3-year-overall survival did not differ significantly, time to treatment was significantly shorter in the del(14q) cohort (21·0 months vs. 80·1 months, P = 0·015). In conclusion, the del(14q) is a rare recurrent alteration in diverse mature B-cell neoplasms, shows variable size but distinct clustering of breakpoints, and is associated with short time to treatment.
authors.affiliation: Munich Leukemia Laboratory, Munich Interdisciplinary Clinic for Stem Cell Transplantation, Max-Lebsche-Platz 31, Munich, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Reindl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Frank
authors.initials: F
authors.lastname: Dicker
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D015463:Leukemia, Prolymphocytic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region