Subject(s)
Gene Expression , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Positive Regulatory Domain I-Binding Factor 1/genetics , Biomarkers , Biopsy , Female , Humans , Immunohistochemistry , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Male , Neoplasm Grading , Positive Regulatory Domain I-Binding Factor 1/metabolism , Protein IsoformsABSTRACT
We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.
Subject(s)
Chromosome Aberrations , Lymphoma, B-Cell, Marginal Zone/genetics , Splenic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , DNA, Neoplasm/genetics , Female , Genes, p53 , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , In Situ Hybridization, Fluorescence , Karyotyping , Lymphoma, B-Cell, Marginal Zone/pathology , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Splenic Neoplasms/pathology , Survival RateABSTRACT
We describe a progressive mantle cell lymphoma (MCL) in which multicolor fluorescence in situ hybridization (M-FISH) on metaphases did not detect the characteristic t(11;14)(q13;q32), although translocations of chromosomes 11 with 15, and 14 with 15 were observed. When CCND1/IGH probes were hybridized to metaphases, however, cryptic fusion signals were detected on the der(11) and der(14) sites of CCND1 (11q13) and IGH (14q32), revealing a complex translocation involving chromosomes 11, 14, and 15. Interphase FISH with CCND1/IGH probes revealed varying patterns with one or two fusion signals, and some with no clear evidence of fusion. Loss of 17p and gain of 3q, known to be associated with disease progression in MCL, were detected with M-FISH and confirmed with the use of p53 and BCL6 probes together with comparative genomic hybridization, which detected also an interstitial deletion on 7p21. This case further illustrates the value of M-FISH in combination with fusion probes in elucidating complex cytogenetic abnormalities.
