Dic(17;18)(p11.2;p11.2) is a recurring abnormality in chronic lymphocytic leukaemia associated with aggressive disease
Open Access
- 9 February 2010
- journal article
- Published by Wiley in British Journal of Haematology
- Vol. 148 (5), 754-759
- https://doi.org/10.1111/j.1365-2141.2009.08007.x
Abstract
Interphase cytogenetics are commonly used to identify clonal abnormalities in chronic lymphocytic leukemia (CLL) patients but fail to identify recurrent translocations that ultimately can direct more focused molecular characterization. Given the importance of del(17p13.1) in CLL outcome, we performed an extensive review of 1213 patients undergoing metaphase cytogenetics at our institution and identified 16 (1·3%) with a recurrent unbalanced translocation between the p arms of chromosomes 17 and 18 that results in a dicentric chromosome with loss of much of 17p and 18p. The dic(17;18)(p11.2;p11.2) was associated with a complex (three or more unrelated cytogenetic abnormalities) karyotype in 12 patients (75%) at the time that the abnormality was first identified, and eventually associated with a complex karyotype in 94% of patients. IGHV mutational analysis was un‐mutated in 88% of cases where evaluation was possible. Except for one patient who was diagnosed with CLL incidentally during a workup for metastatic tonsillar cancer, all patients identified with dic(17;18)(p11.2;p11.2) met criteria for disease treatment, with a median time from diagnosis to first treatment of 15 months. Our data demonstrate that dic(17;18)(p11.2;p11.2) is a novel recurrent cytogenetic abnormality in CLL associated with early age at diagnosis and accelerated disease progression. Future efforts to identify genes disrupted by this translocation are warranted and ongoing.Keywords
This publication has 35 references indexed in Scilit:
- Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribineLeukemia, 2007
- Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997Journal of Clinical Oncology, 2007
- Loss of TP53 is due to rearrangements involving chromosome region 17p10∼p12 in chronic lymphocytic leukemiaCancer Genetics and Cytogenetics, 2006
- Select High-Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy With Fludarabine and Rituximab in Chronic Lymphocytic Leukemia: Justification for Risk-Adapted TherapyJournal of Clinical Oncology, 2006
- Binet’s Staging System and VH Genes Are Independent but Complementary Prognostic Indicators in Chronic Lymphocytic LeukemiaJournal of Clinical Oncology, 2003
- More extensive genetic alterations in unmutated than in hypermutated cases of chronic lymphocytic leukemiaGenes, Chromosomes and Cancer, 2003
- Genome Architecture Catalyzes Nonrecurrent Chromosomal RearrangementsAmerican Journal of Human Genetics, 2003
- Genomic Aberrations and Survival in Chronic Lymphocytic LeukemiaNew England Journal of Medicine, 2000
- Cytogenetic Findings and Survival in B-cell Chronic Lymphocytic Leukemia. Second IWCCLL Compilation of Data on 662 PatientsLeukemia & Lymphoma, 1991
- Prognostic Subgroups in B-Cell Chronic Lymphocytic Leukemia Defined by Specific Chromosomal AbnormalitiesNew England Journal of Medicine, 1990