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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

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Cosson, Adrien Chapiro, Elise Belhouachi, Nabila Cung, Hong-Anh Keren, Boris Michaux, Lucienne [UCL] Groupe Francophone de Cytogénétique Hématologique

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2014
Language Anglais
Journal information "Genes, Chromosomes & Cancer" - Vol. 53, no.8, p. 657-666 (2014)
Peer reviewed yes
Publisher Wiley-Liss ((United States) New York, NY)
issn 1045-2257
e-issn 1098-2264
Publication status Publié
Affiliation UCL - (SLuc) Service d'hématologie
MESH Subject Adult ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Mutation ; Receptor, Notch1 ; Trisomy ; Aged ; Aged, 80 and over ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 14 ; Female ; Humans ; Immunoglobulin Heavy Chains ; Immunoglobulin Variable Region
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Bibliographic reference Cosson, Adrien ; Chapiro, Elise ; Belhouachi, Nabila ; Cung, Hong-Anh ; Keren, Boris ; et. al. 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma. In: Genes, Chromosomes & Cancer, Vol. 53, no.8, p. 657-666 (2014)
Permanent URL http://hdl.handle.net/2078.1/154523