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14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma
Author(s) -
Cosson Adrien,
Chapiro Elise,
Belhouachi Nabila,
Cung HongAnh,
Keren Boris,
Damm Frederik,
Algrin Caroline,
Lefebvre Christine,
FertFerrer Sandra,
Luquet Isabelle,
Gachard Nathalie,
Mugneret Francine,
Terre Christine,
CollongeRame MarieAgnes,
Michaux Lucienne,
RafdordWeiss Isabelle,
Talmant Pascaline,
Veronese Lauren,
Nadal Nathalie,
Struski Stephanie,
Barin Carole,
Helias Catherine,
Lafage Marina,
Lippert Eric,
Auger Nathalie,
Eclache Virginie,
RoosWeil Damien,
Leblond Veronique,
Settegrana Catherine,
Maloum Karim,
Davi Frederic,
MerleBeral Helene,
Lesty Claude,
NguyenKhac Florence
Publication year - 2014
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22176
Subject(s) - ighv@ , chronic lymphocytic leukemia , trisomy , biology , fluorescence in situ hybridization , cancer research , leukemia , chromosome , genetics , gene
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%), del TP53 (11/80, 14%) del ATM (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. © 2014 Wiley Periodicals, Inc.