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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A gene locus for ataxia-telangiectasia (A-T) is in chromosome region 11q22 to 11q23 and predisposes to cancer. Ataxia-telangiectasia patients appear to have two separate clinical patterns of malignancy. One pattern involves solid tumors, which have not been stressed and which include malignancies in the oral cavity, breast, stomach, pancreas, ovary, and bladder. Detection of a solid tumor in an A-T patient should serve as a warning. It heralds a markedly elevated risk of another malignancy in that patient. The second pattern of neoplasia in A-T is well recognized and consists of lymphocytic leukemia and non-Hodgkin's lymphoma. These malignancies may relate to immunodeficiency in A-T and to chromosome breakage and rearrangement, which are a feature of A-T. These two patterns of malignancy may be truly separate and reflect different mechanisms of malignancy in A-T, or they may not really be separate but instead reflect a single mechanism of malignancy. The situation in A-T is reminiscent of that in the acquired immunodeficiency syndrome (AIDS), in which Kaposi's sarcoma occurs with mild immunodeficiency and pneumocystis carinii pneumonia occurs with more profound immunodeficiency owing to the human immunodeficiency virus. Next to pulmonary disease, cancer is the leading cause of death in A-T.
Cancer Genet Cytogenet 1990 May
PMID:Cancer in ataxia-telangiectasia patients. 218 34

The genetic factors involved in the multistep process of carcinogenesis can be divided at least into two major categories: 1. Mutated or lost genes, which may directly represent one step in the sequential process (tumour suppressor genes); inheritance of one tumour suppressor gene causes dominant expression of the carcinogenic phenotype (the dominant inheritance is described in the accompanying paper); 2. Other genes, which lead to conditions that favour the development of cancer and generally are inherited in a recessive fashion; they are the subject of this paper. Autosomal recessively inherited diseases, such as xeroderma pigmentosum, ataxia-telangiectasia, Bloom's syndrome and Fanconi's anaemia display increased genome instability (chromosomal fragility and/or DNA-repair deficiencies) and are associated in the homozygote and probably also in the heterozygote state with defined malignancies. Neoplasms particularly of the lymphoreticular system frequently occur in patients with genetically determined immunodeficiencies (e.g. severe combined immune deficiency or Wiskott-Aldrich syndrome). People differ due to their individual genetic constitution in their responses to various classes of carcinogens such as physical and chemical agents, to dietary habits, as well as to viruses. Furthermore, tumours are often found in patients displaying premature aging (e.g. Werner's syndrome). In addition, several metabolic abnormalities such as genetic syndromes featuring chronic liver disease, but also many other inherited metabolic conditions have cancer as a regular or frequent complication.
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PMID:Recessively inherited deficiencies predisposing to cancer. 219 May 29

Ataxia-telangiectasia (A-T) is an autosomal recessive syndrome whose principal features are progressive cerebellar ataxia, oculocutaneous telangiectasia, varied immune defects, a high cancer incidence, and clinical and cellular sensitivity to ionizing radiation and certain radiomimetic compounds. Cell and chromosome complementation studies have provided some evidence that mutations leading to the A-T phenotype may have occurred at more than one locus. Mapping with DNA polymorphisms has localized the predominant A-T mutation to chromosome 11q22-23. Heterozygous carriers of an A-T allele constitute about 1% of the United States population and are at a high risk for certain cancers, most notably female breast cancer. Cloning of the A-T allele(s) will assist in the early or prenatal diagnosis of A-T and provide a firm basis for determining who, in the general population, carries this gene and is therefore at a high risk of cancer.
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PMID:Genetic aspects of ataxia-telangiectasia. 219 11

The object of this study was to determine whether ataxia-telangiectasia (AT) cells are more sensitive than normal cells to reduced oxygen species generated either during normal cell processes or resulting from metabolism of xenoblotics. To test this hypothesis four AT and four normal fibroblast cultures were exposed to hydrogen peroxide (H2O2) and the induction of micronucleated cells was assayed. AT cultures responded to the H2O2 treatment with a greater increase in micronucleus frequencies than that observed in normal cultures (P less than 0.01). At time course study showed that an elevation in micronucleus frequencies occurred earlier in AT cultures (significant increase by 1.5 h after treatment) than in normal cultures, possibly indicating a G2-phase sensitivity of AT cells to H2O2. The addition of an aqueous extract of areca nut to the cultures, as an example of exogenous stress, induced a greater frequency of micronucleated cells in AT cultures than in the normal cultures. These results suggest that the AT syndrome may serve as a model for investigating the role of reduced oxygen species in cancer.
Cancer Lett 1990 Oct 08
PMID:Response of fibroblast cultures from ataxia-telangiectasia patients to oxidative stress. 220 88

Cancer incidence was measured retrospectively in 574 close blood relatives of white ataxia-telangiectasia (A-T) patients and 213 spouse controls in 44 previously unreported families. The cancer incidence rate in the adult blood relatives was significantly elevated over the rate in the spouse controls (rate ratio = 3.9, p less than 0.01). For heterozygous carriers of the A-T gene, the relative risk of cancer was estimated to be 6.1 (p less than 0.005) as compared with nonheterozygotes. The most frequent cancer site in the blood relatives was the female breast, with nine cancers observed. These findings provide further support for the hypothesis that heterozygotes for the A-T gene are predisposed to cancer.
Cancer Genet Cytogenet 1990 Nov 01
PMID:Cancers in 44 families with ataxia-telangiectasia. 225 79

The phenomenon of sister chromatid exchange (SCE) is an interesting genetic event in metaphase chromosomes, even though its exact mechanism remains unknown. The fact that SCE can take place, whether "spontaneously" or induced by various agents, is in itself important, for such an event, involving damage and possible repair of bilateral loci in chromosomes, presents opportunities for modification of the chromosomal structure and/or function (e.g., oncogene activation). It has been assumed that under "normal" circumstances, SCE does not lead to any change in the functional genome, although this may not apply to abnormal conditions. The latter may be produced by a number of chemical agents (including various carcinogens) that lead to a significantly increased incidence of SCE in normal and malignant cells either in vitro or in vivo. In fact, SCE has been recognized and advocated as a most sensitive test for potentially mutagenic and/or carcinogenic agents. Thus, the broad field of SCE studies becomes of direct interest for and subject to exploration by those involved with cancer causation and biology. In this review, a synopsis of our experiences with high SCE mechanisms in Bloom syndrome cell lines will be presented, in connection with high SCE mutant cell line derived from ataxia telangiectasia (AT) and/or malignant transformation.
Cancer Genet Cytogenet 1990 Dec
PMID:Nature and role of high sister chromatid exchanges in Bloom syndrome cells. Some cytogenetic and immunological aspects. 226

Patients who are homozygous for ataxia-telangiectasia (AT) have an exceptionally high incidence of cancer. Heterozygous individuals for the disease have been reported to be at an increased risk of cancer, particularly breast cancer in female carriers. We have analyzed eight Norwegian families with AT for cancer incidence in the parents, in the parents' sibs, grandparents, and grandparents' sibs. Two of the obligate heterozygote females have had premenopausal breast cancer. This incidence is significantly higher than expected for that group. No increase in the cancer incidence was observed in the parents' sibs, the grandparents, or the grandparents' sibs. Since the incidence of AT is low, data from many sources have to be combined to allow any conclusion.
Genes Chromosomes Cancer 1990 Nov
PMID:Breast cancer and other cancers in Norwegian families with ataxia-telangiectasia. 226 81

Two breakpoints within chromosome 11q23 were characterized with 29 DNA probes to establish a physical map of the region. This region is notable in that it contains at least 14 functional genes which are also syntenic in the mouse (chromosome 9). Chromosome 11q23 includes these markers: STMY, CLG, NCAM, DRD2, APOA1, APOC3, APOA4, CD3E, CD3D, CD3G, PBGD, THY1, ets-1, and cbl-2. The two breakpoints, herein called "X;11" and "4;11," defined a region of approximately 8 cM containing the APO and CD3 complexes as well as the polymorphic marker D11S29. DRD2 localized centromeric to the X;11 breakpoint despite evidence for close genetic linkage to D11S29, suggesting that DRD2 lies close to the X;11 breakpoint. THY1, PBGD, and cbl-2 localized telomeric to the 4;11 breakpoint and thus to the [D11S29--APO--CD3] grouping as well. The physical map helps to correlate the cytogenetic and linkage maps of this region. It also suggests that the human 11q23 syntenic grouping is inverted with respect to its murine counterpart. Based on this physical map and on our primary linkage map of the 11q23 region, we are able to confirm a preliminary localization of the gene for ataxia-telangiectasia group A (ATA) to a region centromeric to the interval defined by D11S144 (pYNB3.12) and THY1.
Cancer Genet Cytogenet 1990 May
PMID:Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus. 233 77

Deoxyribonucleoside triphosphate (dNTP) pool sizes were determined in cell strains derived from patients with the genetic diseases ataxia telangiectasia (GM2052), Bloom's syndrome (GM1492), and Fanconi's anemia (GM368), and were compared to the dNTP pools in a normal human fibroblast cell strain (253/79). In addition, the effect of deoxythymidine on both dNTP pool levels and cell growth was examined. The three mutant cell strains differed only slightly from the normal cell strain. The cellular characteristics of the cell strains, such as chromosome instability, are apparently not an effect of dNTP pool imbalance.
Cancer Biochem Biophys 1990 Jan
PMID:Deoxyribonucleoside triphosphate pool levels in three cell strains of human chromosome instability syndromes: ataxia telangiectasia (GM2052), Bloom's syndrome (GM1492), and Fanconi's anemia (GM368). 233 82

We have collected and studied the genealogical data of 8 patients with the autosomal recessive syndrome of microcephaly, normal intelligence, immunodeficiency, risk of malignancy and chromosomal instability resembling ataxia telangiectasia (AT), but different in complementation group. 50% of our probands died from lymphoreticular malignancies in early childhood. We have found a significantly increased incidence of malignant tumors in 142 blood relatives as compared with a control group of 87 spouses. All patients belonged to the same complementation group differing from the 5 known AT complementation groups, which seems to be in general more malignant than all other groups of AT. From this standpoint our material is homogeneous in contrast to other similar studies in AT families. We think this syndrome represents another model to examine the relationship between genetic background, chromosomal abnormalities, immunodeficiency and cancer development.
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PMID:An increased risk for malignant neoplasms in heterozygotes for a syndrome of microcephaly, normal intelligence, growth retardation, remarkable facies, immunodeficiency and chromosomal instability. 234 14


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