DETECTION OF 14Q32.33 TRANSLOCATION AND T(11-14) IN INTERPHASE NUCLEIOF CHRONIC B-CELL LEUKEMIA LYMPHOMAS BY IN-SITU HYBRIDIZATION/

Abnormalities of chromosome 14 involving band q32.33 are among the mos t commonly observed cytogenetic alterations in B-cell malignancies. To assess the incidence and pathogenetic implications of 14q32.33 transl ocation in chronic B-cell leukemia/lymphomas, we performed fluorescenc e in situ hybridization (FISH) analysis with variable region (V-H) and gamma constant region (C gamma) gene probes in 37 patients with these disorders. Chromosome 14q32.33 translocation was detected in 2 of 18 patients with chronic lymphocytic leukemia (CLL), 1 of 2 with CLL of m ixed cell types (CLL/PL), 1 of 2 with pro-lymphocytic leukemia (PLL), 5 of 6 with leukemic mantle-cell lymphoma (MCL), 2 of 7 with splenic B -cell leukemia/lymphoma of possible marginal zone origin (SBLL) and 2 with leukemic follicular lymphoma (FL). To further characterize 14q32. 33 translocations in these patients, we developed a new procedure usin g double-color FISH with PRAD1, BCL2, V-H and C gamma gene probes. Chr omosome t(11;14) was detected in 1 patient with CLL/PL, 1 with PLL and 5 with MCL. Chromosome t(14;18) was detected in 2 patients with FL. I n a PLL patient with t(11;14), the cosmid CPP29 containing the PRAD1 g ene and its 5'-flanking region split and co-localized with both C gamm a and V-H gene probes, thus spanning the breakpoint. In CLL and SBLL p atients, donor chromosomes were other than chromosomes 2, 11, 18 and 1 9, suggesting the involvement of a novel oncogene(s) in the pathogenes is of these diseases. Interphase FISH rapidly detected 14q32.33 transl ocation, t(11;14) and t(14;18) in B-cell malignancies with low mitotic activity at the single-cell level, facilitating the correlation of th e molecular features of these translocations with clinical characteris tics. (C) 1997 Wiley-Liss, Inc.