title: 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.
abstract: Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS.
authors.affiliation: INSERM U872, Centre de Recherche des Cordeliers, Paris 6, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Cosson
authors.forename: Elise
authors.initials: E
authors.lastname: Chapiro
authors.forename: Nabila
authors.initials: N
authors.lastname: Belhouachi
authors.forename: Hong-Anh
authors.initials: HA
authors.lastname: Cung
authors.forename: Boris
authors.initials: B
authors.lastname: Keren
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.forename: Caroline
authors.initials: C
authors.lastname: Algrin
authors.forename: Christine
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Sandra
authors.initials: S
authors.lastname: Fert-Ferrer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Luquet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gachard
authors.forename: Francine
authors.initials: F
authors.lastname: Mugneret
authors.forename: Christine
authors.initials: C
authors.lastname: Terre
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Collonge-Rame
authors.forename: Lucienne
authors.initials: L
authors.lastname: Michaux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rafdord-Weiss
authors.forename: Pascaline
authors.initials: P
authors.lastname: Talmant
authors.forename: Lauren
authors.initials: L
authors.lastname: Veronese
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nadal
authors.forename: Stephanie
authors.initials: S
authors.lastname: Struski
authors.forename: Carole
authors.initials: C
authors.lastname: Barin
authors.forename: Catherine
authors.initials: C
authors.lastname: Helias
authors.forename: Marina
authors.initials: M
authors.lastname: Lafage
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Auger
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Damien
authors.initials: D
authors.lastname: Roos-Weil
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Catherine
authors.initials: C
authors.lastname: Settegrana
authors.forename: Karim
authors.initials: K
authors.lastname: Maloum
authors.forename: Frederic
authors.initials: F
authors.lastname: Davi
authors.forename: Helene
authors.initials: H
authors.lastname: Merle-Beral
authors.forename: Claude
authors.initials: C
authors.lastname: Lesty
authors.forename: Florence
authors.initials: F
authors.lastname: Nguyen-Khac
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051881:Receptor, Notch1 / Q000235:genetics*; D014314:Trisomy / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1