In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 6 ( 2000-03-14), p. 2773-2778
Abstract:
In mantle cell lymphoma (MCL), the translocation t(11;14) is
considered the cytogenetic hallmark of the disease. Recently, however, deletion of the chromosomal region 11q22-q23 has been identified as a
frequent event in this type of cancer, indicating the existence of a pathogenically relevant tumor suppressor gene in this region. The
deleted segment contains the ATM (ataxia telangiectasia
mutated) gene. ATM is an interesting candidate as a
tumor suppressor gene because constitutive inactivation of the gene predisposes ataxia telangiectasia patients to lymphoid malignancies. To
assess the potential involvement of the gene in MCL lymphomagenesis, we performed mutation analysis of ATM in 12 sporadic cases
of MCL, 7 of them with a deletion of one ATM gene copy,
by using single-strand conformation polymorphism analysis of reverse transcription–PCR-amplified mRNA and subsequent DNA sequencing. In all
seven cases containing a deletion of one ATM allele, a
point mutation in the remaining allele was detected, which resulted in aberrant transcript splicing, truncation, or alteration of the protein.
In addition, biallelic ATM mutations were identified in
two MCLs that did not contain 11q deletions. Interestingly, in three cases analyzed, the ATM mutations detected in the tumor
cells were not present in nonmalignant cells, demonstrating their somatic rather than germ-line origin. The inactivation of both alleles
of the ATM gene by deletion and deleterious point mutation
in the majority of cases analyzed indicates that ATM plays a role in the initiation and/or progression of MCL.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.050400997
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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