Molecular characterization of 11q deletions points to a pathogenic role ofthe ATM gene in mantle cell lymphoma

Deletions involving the long arm of chromosome 11 (11q) have been recently found as recurrent chromosome aberrations in mantle cell lymphoma (MCL). In the current study, the incidence and molecular extent of 11q deletions wer e analyzed in a series of 81 MCL by fluorescence in situ hybridization with probes from a contiguous set of yeast artificial chromosomes (YACs). Loss of chromosome 11 material was observed in 37 of 81 cases (46%), The minimal ly deleted segment comprised YAC 801e11 containing the ATM gene. To further narrow the minimal region of loss, P1-derived artificial chromosomes mappi ng to the critical region were isolated and used as probes in cases without aberrations detectable with YACs, This allowed the identification of an AT M deletion that was beyond the resolution of YAC probes. The identification of a minimally deleted segment affecting ATM suggests a pathogenic role of ATM as a tumor suppressor gene in MCL. (C) 1999 by The American Society of Hematology.