Linked Life Data

10026998

Source:http://linkedlifedata.com/resource/pubmed/id/10026998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-3-5
pubmed:abstractText
The ataxia telangiectasia (A-T) gene, ATM, predisposes affected homozygotes to a wide range of malignancies. It has been suggested that this is a consequence of the genomic instability associated with the syndrome. The elevated risk of malignancy is not, however, observed among A-T heterozygotes (except, apparently, regarding breast cancer). In this report we describe results from the study of the rare sporadic disease, T cell prolymphocytic leukaemia (T-PLL). In all individuals tested, we observed that at least one ATM allele was disrupted by rearrangement, that in many cases both alleles were disrupted and that there were additional mutations, predominantly missense, that clustered toward the 3' end of the gene corresponding to the protein's phosphatidylinositol 3-kinase (PIK)-related domain. We conclude that the ATM gene can act as a tumour suppressor in the development of sporadic T-PLL. Our finding of a surfeit of mutations within ATM may reflect the involvement of the gene at more than one step in tumorigenesis. In particular, we suggest that the clustering of missense mutations may pertain to the late-onset character of both sporadic and A-T-related T-PLL, since the closest homologue of Atm protein is the yeast TEL1 protein that maintains telomere length. ATM inactivation may not be the initiating event in T-PLL tumorigenesis: prior mutation of another gene--perhaps TCL1 activation--may be obligate. This would explain the recessive character of T-PLL risk in A-T.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0080-0015
pubmed:author
pubmed:issnType
Print
pubmed:volume
154
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
156-73
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The ataxia telangiectasia gene in familial and sporadic cancer.
pubmed:affiliation
Department of Haematology and Cytogenetics, Haddow Laboratories, Sutton, Surrey, UK.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't