Cosson Adrien, Chapiro Elise, Belhouachi Nabila, Cung Hong-Anh, Keren Boris, Damm Frederik, Algrin Caroline, Lefebvre Christine, Fert-Ferrer Sandra, Luquet Isabelle, Gachard Nathalie, Mugneret Francine, Terre Christine, Collonge-Rame Marie-Agnes, Michaux Lucienne, Rafdord-Weiss Isabelle, Talmant Pascaline, Veronese Lauren, Nadal Nathalie, Struski Stephanie, Barin Carole, Helias Catherine, Lafage Marina, Lippert Eric, Auger Nathalie, Eclache Virginie, Roos-Weil Damien, Leblond Veronique, Settegrana Catherine, Maloum Karim, Davi Frederic, Merle-Beral Helene, Lesty Claude, Nguyen-Khac Florence
INSERM U872, Centre de Recherche des Cordeliers, Paris 6, France.
Genes Chromosomes Cancer. 2014 Aug;53(8):657-66. doi: 10.1002/gcc.22176. Epub 2014 Apr 12.
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.
14号染色体长臂缺失[del(14q)]在成熟B细胞肿瘤中罕见但反复出现，尤其是在慢性淋巴细胞白血病（CLL）中。为进一步明确这一异常，我们研究了81例del(14q)病例：54例CLL和27例小淋巴细胞淋巴瘤（SLL），这是迄今为止报道病例数最多的系列研究。采用核型分析和荧光原位杂交（FISH）技术，最常见的附加异常是12号染色体三体（tri12），在28/79（35%）的病例中观察到，其次是del13q14（12/79，15%）、delTP53（11/80，14%）、delATM（5/79，6%）和del6q21（3/76，4%）。41/53（77%）的患者IGHV基因未发生突变，IGHV1-69的频率较高（21/52，40%）。14/45（31%）的患者NOTCH1基因发生突变。CLL和SLL在细胞遗传学和分子异常方面无显著差异。使用FISH和单核苷酸多态性阵列（SNP-array）进行的研究表明，14q缺失的大小存在异质性。然而，在48%的病例中发现了一组具有相同del(14)(q24.1q32.33)的病例。在该组中，tri12（P = 0.004）和NOTCH1突变（P = 0.02）的发生率明显高于其他患者。在伴有del(14q)的CLL患者中，无治疗生存期（TFS）的中位数为27个月。总之，del(14q)与tri12以及不良预后因素相关：IGHV基因未突变（IGHV1-69基因库过度表达）、NOTCH1突变和较短的TFS。
