PMID- 10397742
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 2
DP  - 1999 Jul 15
TI  - Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic
      lymphocytic leukemia.
PG  - 748-53
AB  - Deletion in chromosome bands 11q22-q23 is one of the most common chromosome
      aberrations in B-cell chronic lymphocytic leukemia (B-CLL). It is associated with
      extensive lymph node involvement and poor survival. The minimal consensus
      deletion comprises a segment, which contains the ATM gene presenting an
      interesting candidate gene, as mutations in ATM predispose A-T patients to
      lymphoid malignancies. To investigate a potential pathogenic role of ATM in
      B-cell tumorigenesis, we performed mutation analysis of ATM in 29 malignant
      lymphomas of B-cell origin (B-CLL = 27; mantle cell lymphoma, [MCL] = 2).
      Twenty-three of these carried an 11q22-q23 deletion. In five B-CLLs and one MCL
      with deletion of one ATM allele, a point mutation in the remaining allele was
      detected, which resulted in aberrant transcript splicing, alteration, or
      truncation of the protein. In addition, mutation analysis identified point
      mutations in three cases without 11q deletion: two B-CLLs with one altered allele
      and one MCL with both alleles mutated. In four cases analyzed, the ATM
      alterations were not present in the germ line indicating a somatic origin of the 
      mutations. Our study demonstrates somatic disruption of both alleles of the ATM
      gene by deletion or point mutation and thus its pathogenic role in sporadic
      B-cell lineage tumors.
FAU - Schaffner, C
AU  - Schaffner C
AD  - Abteilung "Organisation komplexer Genome", Deutsches Krebsforschungszentrum,
      Heidelberg, Germany.
FAU - Stilgenbauer, S
AU  - Stilgenbauer S
FAU - Rappold, G A
AU  - Rappold GA
FAU - Dohner, H
AU  - Dohner H
FAU - Lichter, P
AU  - Lichter P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Ataxia Telangiectasia/complications/genetics
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle Proteins
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Chromosomes, Human, Pair 11/*genetics/ultrastructure
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/genetics
MH  - DNA-Binding Proteins
MH  - Exons/genetics
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/pathology
MH  - Lymphoma, B-Cell/genetics
MH  - *Point Mutation
MH  - *Protein Serine-Threonine Kinases
MH  - Proteins/*genetics/physiology
MH  - *Sequence Deletion
MH  - Tumor Suppressor Proteins
EDAT- 1999/07/09 00:00
MHDA- 1999/07/09 00:01
CRDT- 1999/07/09 00:00
PHST- 1999/07/09 00:00 [pubmed]
PHST- 1999/07/09 00:01 [medline]
PHST- 1999/07/09 00:00 [entrez]
AID - S0006-4971(20)67464-X [pii]
PST - ppublish
SO  - Blood. 1999 Jul 15;94(2):748-53.