Ataxia telangiectasia genes and predisposition to leukaemia, lymphoma and breast cancer

Taylor, Alexander M.

doi:10.1038/bjc.1992.208

Cited by 65 publications

(26 citation statements)

References 33 publications

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“…In line with the finding that A-T patients have a weak immune system, the most common malignancy linked with A-T patients is that of immune system (Leukemias and Lymphomas) with the most common being non-Hodgkin's lymphoma (~45%) [152] followed by acute lymphocytic leukemias (~20%) [153]. This link has further been demonstrated by…”

Section: Cancer Predispositionsupporting

confidence: 60%

ATM in focus: A damage sensor and cancer target

Khalil¹,

Tummala²,

Zhelev³

2012

Biodiscovery

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The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxia-telangiectasia mutated (ATM) protein kinase as a damage sensor and its potential as therapeutic target for treating cancer. This monograph discusses DNA repair mechanisms activated after DNA doublestrand breaks (DSBs), i.e. non-homologous end joining, homologous recombination and single strand annealing and the role of ATM in the above types of repair. In addition to DNA repair, ATM participates in a diverse set of physiological processes involving metabolic regulation, oxidative stress, transcriptional modulation, protein degradation and cell proliferation. Full understanding of the complexity of ATM functions and the design of therapeutics that modulate its activity to combat diseases such as cancer necessitates parallel theoretical and experimental efforts. This could be best addressed by employing a systems biology approach, involving mathematical modelling of cell signalling pathways.

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Section: Cancer Predispositionsupporting

confidence: 60%

ATM in focus: A damage sensor and cancer target

Khalil¹,

Tummala²,

Zhelev³

2012

Biodiscovery

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“…In the literature, there are reports of an increased incidence of cancer in patients with AT [3]. Of all AT patients, 10% develop cancer and lymphomas, 80% before the 15th year of life [2]. Specifically, lymphomas (41%), leukaemias (23%), and solid tumors (26%) of the stomach, CNS, ovary, and uterus have been described [3].…”

mentioning

confidence: 97%

“…This syndrome, called ataxiatelangiectasia (AT), is inherited in an autosomalrecessive manner, with an incidence of about 1:300,000 live births [1,2]. Most of the patients die within the second decade of life from pulmonary disease [3].…”

mentioning

confidence: 99%

Fatal outcome in two girls with Hodgkin disease complicating ataxia-telangiectasia (Louis-Bar syndrome) despite favorable response to modified-dose chemotherapy

Irsfeld

Krholz

Janen

et al. 2000

Med. Pediatr. Oncol.

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“…ATM homozygotes develop various malignancies, particularly leukemias and lymphomas (reviewed in Taylor et al, 1996). ATM heterozygotes are already known to be at an increased risk of breast cancer, although the risk for other cancers remains less clear (Taylor, 1992). Germline mutations have been detected in a handful of patients with B-CLL suggesting a link between ATM heterozygosity and genetic predisposition to B-CLL (Bullrich et al, 1999;Stankovic et al, 1999).…”

Section: Chromosomal Defects In B-cll and Implicated Genesmentioning

confidence: 99%

Genetic alteration associated with chronic lymphocytic leukemia

Cotter

Auer²

2007

Cytogenet Genome Res

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The genetics of B-cell chronic lymphocytic leukemia (B-CLL) differ considerably from most other forms of hematologic malignancy which are usually characterized by chromosome translocations. B-CLL typically contains chromosomal deletions and chromosomes 13q14 and 11q22→q23 are the most common. These two regions appear to share a common ancestral origin (Auer et al., 2007b). Overall, chromosomal abnormalities can be found in the majority of patients with B-CLL when using sensitive techniques (Dohneret al., 2000) and possibly reflects an underlying predisposition, with a small but significant number of familial cases. Although single and consistent abnormalities are most common, multiple rearrangements can occur, often with disease progression (Feganetal., 1995; Dohner et al., 2000). Regions of recurrent deletion suggest the presence of tumor suppressor genes if following Knudson’s theoretical 2-hit model. However, despite extensive sequencing analysis over the last decade and lack of pathogenic mutations identified, there has been a move away from this suggested hypothesis and alternative mechanisms of gene inactivation involving epigenetic silencing or haploinsufficiency may be considered as more likely in this disease. This review focuses on the common genetic abnormalities in B-CLL and relates them to some of the more recent hypotheses on inactivation of genes within these regions of deletion.

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Ataxia telangiectasia genes and predisposition to leukaemia, lymphoma and breast cancer

Cited by 65 publications

References 33 publications

ATM in focus: A damage sensor and cancer target

ATM in focus: A damage sensor and cancer target

Fatal outcome in two girls with Hodgkin disease complicating ataxia-telangiectasia (Louis-Bar syndrome) despite favorable response to modified-dose chemotherapy

Genetic alteration associated with chronic lymphocytic leukemia

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