Aspects cytogénétiques de l'ataxie télangiectasie

Aurias, A

doi:10.4267/10608/3510

Cited by 4 publications

(4 citation statements)

References 2 publications

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“…For example, in A-T stable T cells with inv(l4)(qll;q32) or t(l4;14)(qll;q32) are elevated 50-fold over their frequency in normal individuals (Aurias et al 1980). For the record, smaller transient lymphocytoses with inv(7) and t(7;14) clones have also been reported in normal and in A-T (Aurias 1981) The mutator hypothesis is thus an incomplete description of the role of ATM in tumorigenesis. A key test of the mutator hypothesis is whether the gene is occasionally mutated in sporadic cancers.…”

Section: Theories On the Role Of Atm In Tumorigenesismentioning

confidence: 92%

The Ataxia Telangiectasia Gene in Familial and Sporadic Cancer

Yuille

Coignet

1998

Recent Results in Cancer Research

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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 TELl protein that maintains telomere length. ATM inactivation may not be the initiating event in T-PLL tumorigenesis: ·prior mutation of another gene -perhaps TeLl activation -may be obligate. This would explain the recessive character of T-PLL risk in A-T.

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Section: Theories On the Role Of Atm In Tumorigenesismentioning

confidence: 92%

The Ataxia Telangiectasia Gene in Familial and Sporadic Cancer

Yuille

Coignet

1998

Recent Results in Cancer Research

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“…Rearrangements involving band 7q35-q36 have been described in T-cell lymphomas (63), and a gain of chromosome 7 has been reported in human T-cell lymphadenopathy virus (HTLV)-positive leukemia (232). Both clonal and nonclonal rearrangements affecting band 7q35 occur at a high frequency in circulating T cells in patients with the autosomal recessive immunodeficiency disorder ataxia telangiectasia (11,98,165). Deletion of one of the y gene constant regions was reported in three cases of T-cell leukemia (167).…”

Section: Chromosomal Location Of Genes For the T-cell Receptormentioning

confidence: 99%

T-cell clones and T-cell receptors.

Fitch¹

1986

Microbiological Reviews

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“…Karyotyping of peripheral lymphocytes from A-T homozygotes shows nonrandom chromosomal rearrangements which preferentially involve chromosomal breakpoints at 14q11, 14q32, 7q35, 7p14, 2pll, and 22q11, and correlate with the regions of the Tcell and B-cell receptor gene complexes (Aurias, 1986). Telomere shortening and fusions, with normal telomerase activity (Pandita et al, 1995), have been observed in peripheral blood lymphocytes of A-T patients, especially in pre-leukemic T-cell clones (Metcalfe et al, 1996).…”

Section: Cytogenetic Featuresmentioning

confidence: 99%