The ATM gene in the pathogenesis of mantle-cell lymphoma

Background: Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin-D1, but additional chromosomal abnormalities appear to be required for MCL path ogenesis. Patients and methods: Deletions involving chromosome 11q, which were recent ly found as recurrent aberrations in MCL, were analyzed at the molecular le vel in a series of 81 MCL by fluorescence in sills hybridization (FISH) wit h probes from a contiguous set of yeast artificial chromosomes (YACs) spann ing bands 11q14-q24. Results and conclusions: Loss of chromosome 11 material was observed in 37 of the 81 MCL cases (46%). The consensus deletion comprised YAC 801e11 cont aining the ATM gene. The minimal region of loss was further narrowed with P 1-derived artificial chromosome (PAC) probes. This allowed the identificati on of a deletion confined to the genomic region of ATM, which, together wit h intragenic mutations found in the coding sequence. suggests a role of ATM as a tumor suppressor gene in MCL.