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

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. © 1993 Wiley‐Liss, Inc.