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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3262-3264
Molecular Characterization of 11q Deletions Points to a Pathogenic
Role of the ATM Gene in Mantle Cell Lymphoma
Stephan Stilgenbauer,
Dirk Winkler,
German Ott,
Claudia Schaffner,
Elke Leupolt,
Martin Bentz,
Peter Möller,
Hans K. Müller-Hermelink,
Michael R. James,
Peter Lichter, and
Hartmut Döhner
From the Department of Internal Medicine III, University of Ulm, Ulm,
Germany; the Department of Pathology, University of Würzburg,
Würzburg, Germany; Deutsches Krebsforschungszentrum, Heidelberg,
Germany; the Department of Pathology, University of Ulm, Ulm, Germany;
and Wellcome Trust Centre for Human Genetics, Oxford, UK.
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 were 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 minimally deleted segment
comprised YAC 801e11 containing the ATM gene. To further narrow
the minimal region of loss, P1-derived artificial chromosomes mapping
to the critical region were isolated and used as probes in cases
without aberrations detectable with YACs. This allowed the
identification of an ATM 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.
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