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 pathogenesis.


METHODS
Deletions involving chromosome 11q, 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 11q14-q24.


CONCLUSIONS
Loss of chromosome 11 material was observed in 37 of the 81 MCL cases (46%). The consensus deletion comprised YAC 801e11 containing the ATM gene. The minimal region of loss was further narrowed with P1-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.
Stilgenbauer
S
S
Abteilung Innere Medizin III, University of Ulm, Germany.
Schaffner
C
C
Winkler
D
D
Ott
G
G
Leupolt
E
E
Bentz
M
M
Möller
P
P
Müller-Hermelink
H K
HK
James
M R
MR
Lichter
P
P
Döhner
H
H
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins; D005260:Female; D019940:Genes, bcl-1; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases