Dominant negative ATM mutationsn in breast cancer families
Dominant negative ATM mutationsn in breast cancer families
LEI, Haixin, Daria POSP??ILOV?, Arnica LINDBLOM a Igor VO?ECHOVSK?. Dominant negative ATM mutationsn in breast cancer families. Journal of the National Cancer Institute, Bethesda: National Cancer Institute, 2002, ro?. 94, ?. 12, s. 951-952. ISSN .
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Základní údaje
Originální název
Dominant negative ATM mutationsn in breast cancer families
LEI, Haixin (752 ?védsko),
(203 ?eská republika), Arnica LINDBLOM (752 ?védsko) a
(203 ?eská republika, garant).
Journal of the National Cancer Institute, Bethesda, National Cancer Institute, -8874.
Dal?í údaje
Originální jazyk
angli?tina
Typ v?sledku
?lánek v odborném periodiku
Onkologie a hematologie
Stát vydavatele
Spojené státy
není p?edmětem státního ?i obchodního tajemství
Impakt faktor
Impact factor: 14.500
RIV/10/02:
Organiza?ní jednotka
Léka?ská fakulta
Klí?ová slova anglicky
Změnila: Mgr. Daria Strouhalová, Ph.D., u?o 18974. Změněno: 15. 5. .
Breast cancer is the most frequent malignancy in women in the world, with a cumulative lifetime risk estimated to be 10-12%. Cytogenic and molecular genetic analyses of breast tumor cells suggest that the development of human breast cancer involves the accumulation of alterations in genes which normally serve to control growth and differentiation. One type of this alteration is loss of heterozygosity (LOH), which is detected in many cases of breast cancer. LOH of tumor suppressor genes are associated with cancerogenesis. Several studies have indicated that the genes harbors on long arm of chromosome 11, could be detected during tumorogenesis. Deletions at 11q23 were detected in variety of human neoplasma, including breast. In this region can be harbor at least one tumor suppressor gene, which is inactivated during the establishment or progression of several types of tumors. Evidence for the existence of a tumor suppresor gene(s) in this region came from the observation that tumorgenicity of the MCF-7 cell line is inhibited by the introduction of the segment 11q13-q23 of the normal human chromosome 11. One of the candidate gene is A-T (ataxia-teleangiectasia) gene, located at chromosomal region 11q22-q23. Patients carrying two mutant alleles (ATM) and affected by A-T a 100-fold higher risk of developing cancer, moustly leukemias and lymphomas, than unaffected age-matched subjects. Heterozygous A-T carriers have a 3,1 and 2,3 (females and males) fold increases risk of cancer, in particular breast cancer, compared to the normal population. IT is estimated, that asuch as 8% of sporadic breast cancer could possibly develop in carriers of ATM gene predisposition mutations. It seems that inherited mutations in ATM gene are responsible for a certain proportion of breast cancer cases, and that LOH of other allele will unmask such a recessive mutation. The ATM gene spans - 150kb genomic sequence and contains 66 exons. It is expressed as 12 kb transcript in all tissues and cell types. This gene is implicated in cell cycle regulation, control of telomere length, and response to DNA danage. The enzyme cooperates with many protein in cell. Its inactivation could be influenced repair process in cell. We interested in catalytic domain as candidate region for inactivation of kinase activity. This part of protein corresponds with last 16 exons on DNA of this gene. Tumor DNA from 42 patients with primary breast cancer were studied. This samples were choosen after analyzed for lost of one alele (part of chromosome) in region 11q22-q23 by methods which detected polymorphic makers on pair of chromosomes. For LOH detection we used SSCP (single-strand conformation polymorphism) and silver staining method. We did not found any unique SSCP variants.
Návaznosti
MSM , záměrNázev: Molekulární patofyziologie multigenních chorob
Investor: Ministerstvo ?kolství, mláde?e a tělov?chovy ?R, V?zkumné záměry
Zobrazeno: 9. 5.
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An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalip.
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内容提示：An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalipoproteinemia pedigree with three ABCA1 mutations
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An ABCA1 truncation shows no dominant negative eff
官方公共微信Proc Natl Acad Sci U S A. 1996 April 30; 93(9): .
PMCID: PMC39492Dominant-negative p53 mutations selected in yeast hit cancer hot spots., , and
This article has been
other articles in PMC.Clinically important mutant p53 proteins may be tumorigenic through a dominant-negative mechanism or due to a gain-of-function. Examples for both hypotheses however, it remains unclear to what extent they apply to TP53 mutations in general. Here it is shown that the mutational spectrum of dominant-negative p53 mutants selected in a novel yeast assay correlates tightly with p53 mutations in cancer. Two classes of dominant-negative mut the more dominant one affects codons that are essential for the stabilization of the DNA-binding surface of the p53 core domain and for the direct interaction of p53 with its DNA binding sites. These results predict that the vast majority of TP53 mutations leading to cancer do so in a dominant-negative fashion.Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the
(1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for .
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