The ATM gene in the pathogenesis of mantle-cell lymphoma

iWellcome Trust Centre for Human Genetics, Oxford, UK Summary Background: Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(ll;14)(ql3;q32) leading to an overexpression of cyclin-Dl, but additional chromosomal abnormalities appear to be required for MCL pathogenesis. Patients and methods: Deletions involving chromosome llq, which were recently found as recurrent aberrations in MCL, were analyzed at the molecular level in a series of 81 MCL by fluorescence in situ hybridization (FISH) with probes from a contiguous set of yeast artificial chromosomes (YACs) spanning bands Ilql4-q24. Results and conclusions: Loss of chromosome 11 material was observed in 37 of the 81 MCL cases (46%). The consensus deletion comprised YAC 801el 1 containing the ATM gene. The minimal region of loss was further narrowed with Pl-derived artificial chromosome (PAC) probes. This allowed the identification of a deletion confined to the genomic region of ATM, which, together with intragenic mutations found in the coding sequence, suggests a role of ATM as a tumor suppressor gene in MCL.