Cloning of a breakpoint cluster region at band 3q27 involved in human non‐Hodgkin's lymphoma

Abstract

In a previous cytogenetic analysis, we showed the recurrence of translocations involving band 3q27 and immunoglobulin gene regions in 20 out of 319 patients with non-Hodgkin's lymphoma (NHL). We report here the molecular cloning of the translocation breakpoint from tumor cells of a patient (LAR) with t(3;14)(q27;q32) and the isolation of DNA probes which identify a major translocation cluster region (MTC) at band 3q27. A DNA library from LAR tumor cells was screened with a JH probe and several clones were identified corresponding either to a somatic rearrangement of JGH genes (V4-D2-J6-Cμ clonal rearrangement) or to the t(3; 14). Analysis of the t(3; I 4) breakpoint showed that chromosome 3 material was translocated to an inverted 14q32 VH-containing fragment which was itself translocated to the J3 gene. Chromosome 3-assigned probes were used to investigate local DNA rearrangements in a series of NHL with 3q27 translocations. Rearrangements were detected in 13 of 17 patients including 9 of 11 with t(3;14)(q27;q32), I of 2 with t(2;3)(P12;q27), I of 2 with t(3;22)(q27;qII), and 2 of 2 NHL with translocations not involving an IG gene, namely, t(3;4)(q27;pII) and t(3;7)(q27;p12). The finding of this MTC should be useful for diagnostic and prognostic studies and for the identification of a novel oncogene at band 3q27 involved in the development of B cell NHL.