Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia: Clinical and biologic correlations. Issue 12 (10th September 2015)

• Record Type: Journal Article
• Authors: Rigolin, Gian Matteo; del Giudice, Ilaria; Formigaro, Luca; Saccenti, Elena; Martinelli, Sara; Cavallari, Maurizio; Lista, Enrico; Tammiso, Elisa; Volta, Eleonora; Lupini, Laura; Bassi, Cristian; Bardi, Antonella; Sofritti, Olga; Daghia, Giulia; Cavazzini, Francesco; Marinelli, Marilisa; Tavolaro, Simona; Guarini, Anna; Negrini, Massimo; Foà, Robin; Cuneo, Antonio
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 12(2015:Dec.)
• Page Start: 818
• Page End: 826
• Publication Date: 2015-09-10
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22293
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>To clarify whether karyotype aberrations (KA) involving regions not covered by the standard fluorescence in situ hybridization (FISH) panel have independent prognostic relevance, we evaluated KA by conventional cytogenetics in a learning cohort (LC; <italic>n</italic> = 166) and a validation cohort (VC; <italic>n</italic> = 250) of untreated chronic lymphocytic leukemia (CLL) patients. In the VC, novel mitogens were used to improve metaphase generation and <italic>TP53</italic>, <italic>NOTCH1</italic>, and <italic>SF3B1</italic> mutations were assessed. KA undetected by FISH were found in 35 and 35% of the cases in the LC and VC, respectively. In addition to FISH, KA allowed reclassification of 23 and 26% of cases in the LC and VC, respectively, into a higher cytogenetic risk group. By multivariate analysis, both in the LC and VC, KA other than isolated 13q deletion correlated with a shorter time to first treatment (TFT; <italic>P</italic> < 0.001 and 0.003, respectively), while a complex karyotype predicted a worse overall survival (OS, <italic>P</italic> = 0.015 and 0.010, respectively). In the VC, where a comprehensive biologic assessment was performed, a shorter TFT was also predicted by stage (<italic>P</italic> < 0.001), <italic>IGHV</italic> mutational status (<italic>P</italic> = 0.05), and del(17p)/<italic>TP53</italic> mutations (<italic>P</italic> = 0.033) while stage (<italic>P</italic> = 0.023) and del(17p)/<italic>TP53</italic> mutations (<italic>P</italic> = 0.024) independently predicted a shorter OS. FISH results did not independently impact on TFT and OS, in the LC and VC cohorts; this was also the case for <italic>NOTCH1</italic> and <italic>SF3B1</italic> mutations in the VC. We suggest that in CLL, conventional karyotyping with novel mitogens could be more effective than FISH for the detection of KA allowing for a more precise refinement of prognosis. © 2015 Wiley Periodicals, Inc.</p> </abstract>