Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: Different genetic mechanisms but equivalent poorer clinical outcome |
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| Authors: | Anna Puiggros Marta Venturas Marta Salido Gonzalo Blanco Concepcin Fernandez‐Rodriguez Rosa Collado Alberto Valiente Neus Ruiz‐Xivill Ana Carri Francisco Jos Ortuo Elisa Luo María Jos Calasanz María Teresa Ardanaz María ngeles Pin Elisabet Talavera María Teresa Gonzlez Margarita Ortega Isabel Marugn Ana Ferrer Eva Gimeno Beatriz Bellosillo Julio Delgado Jos ngel Hernndez Jesús María Hernndez‐Rivas Blanca Espinet |
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| Institution: | 1. Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain;2. Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Res Program, IMIM‐Hospital del Mar, Barcelona, Spain;3. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain;4. Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, Cancer Res Program, IMIM‐Hospital del Mar, Barcelona, Spain;5. Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain;6. Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain;7. Servei d'Hematologia, Institut Català d'Oncologia‐Hospital Universitari Germans Trias i Pujol, IJC, Badalona, Spain;8. Secció d'Hematopatologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain;9. Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain;10. Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain;11. Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain;12. Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain;13. Servicio de Hematología, Hospital de Cruces, Bilbao, Spain;14. Unitat Citogenètica Laboratori Clínic ICS Lleida, Hospital Universitari Arnau de Vilanova, Lleida, Spain;15. Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain;16. Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain;17. Servicio de Hematología y Oncología Médica, Hospital Clínico Universitario, Valencia, Spain;18. Servei d'Hematologia, Hospital del Mar, Barcelona, Spain;19. Laboratori de Biologia Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain;20. Servicio de Hematología, Hospital Universitario Infanta Leonor, Madrid, Spain;21. Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain |
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| Abstract: | Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G‐banding cytogenetics (CGC) i‐del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) F‐del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i‐del(13q) and F‐del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q‐deleted nuclei did not differ from i‐del(13q) patients (73% vs. 64%), but both were significantly higher than F‐del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1 involvement was significantly higher in the i‐del(13q) group (79%, P < 0.001). Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in t(13q) and i‐del(13q) was shorter than F‐del(13q) (67, 44, and 137 months, P = 0.029), and preserved significance in the multivariate analysis. In conclusion, t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q‐deleted CLL patients associated with a worse clinical outcome. © 2014 Wiley Periodicals, Inc. |
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