Novel Gene Mutations In Chronic Lymphocytic Leukemia: Prevalence and Clinical Implications In A Series Of 3185 Cases - Initial Results From The European Research Initiative On CLL
| Autor: | Zadie Davis, David Oscier, Lydia Scarfò, Andreas Agathangelidis, Gianluca Gaidano, Lesley-Ann Sutton, Jitka Malčíková, Šárka Pospíšilová, Kostas Stamatopoulos, Davide Rossi, Jonathan C. Strefford, Diego Cortese, Neus Villamor, Karin E. Smedby, Eugen Tausch, Eva Minga, Gunnar Juliusson, Julio Delgado, Stephan Stilgenbauer, Larry Mansouri, Jana Kminkova, Karla Plevová, Anastasia Hadzidimitriou, Paolo Ghia, Alba Navarro, Antonios M Makris, Richard Rosenquist, Elias Campo, Chrysoula Belessi, Evangelia Stalika, Marta Larrayoz |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
medicine.medical_specialty Univariate analysis Mutation business.industry Incidence (epidemiology) Chronic lymphocytic leukemia Immunology Cell Biology Hematology Gene mutation medicine.disease medicine.disease_cause Bioinformatics Biochemistry Exon Internal medicine medicine Trisomy business IGHV@ |
| Zdroj: | Blood. 122:1614-1614 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | In chronic lymphocytic leukemia (CLL), genomic aberrations identify subgroups of patients with distinct treatment outcomes. In particular, patients with deletion of chromosome 17p and/or TP53 gene mutations have inferior prognosis with standard therapy. Hence, screening for these abnormalities is mandatory prior to enrolling patients in clinical trials (CT) and can be also useful in general practice (GP). Recent studies suggest that aberrant p53 function (p53ab), due to TP53 gene mutations and/or del(17p), is only one of several mechanisms underlying clinical aggressiveness. Indeed, mutations in the NOTCH1, SF3B1 and BIRC3 genes have been reported as recurrent in CLL and correlated to poor outcome which is in contrast to mutations in MYD88. An important caveat stemming from published studies is the relative small and hetereogeneous sample size thus making it difficult to draw conclusions regarding the actual incidence and prognostic relevance of these mutations in CLL. The European Research Initiative on CLL (ERIC) is pursuing several studies to shed light on these issues in large and well-annotated CLL series, comprising both GP CLL and CT CLL cases, and here we report the initial results of this project. To date, a total of 3185 patients have been included in the analysis; 596 (18.7%) are CT cases and 2589 (81.3%) GP cases. Mutational screening provided data on NOTCH1 (entire exon 34 or targeted analysis for del7544-45), TP53 (exons 4-9), SF3B1 (exons 14-16), BIRC3 (exons 6-9) and MYD88 (exon 5). For each gene, almost two-thirds of the cases were analyzed within a year of diagnosis. Overall, BIRC3 and MYD88 mutations were relatively rare [25/923 (2.7%) and 24/1085 (2.2%) respectively], however: (i) BIRC3 mutations were significantly (p Disclosures: Stamatopoulos: Roche: Research Funding. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|