Ignet

Gene Pair Information

Gene Pair: BRCA2, TP53

Related Sentences

#	PMID	Sentence
1	7794027	At the present time, 3 regions of the genome have been implicated in the predisposition to breast cancer in women: the BRCA1 gene, the BRCA2 gene and the TP53 gene.
2	8605112	The major types of genetic abnormalities that are frequently observed in breast tumors are amplification of protooncogenes (MYC, ERBB2) and DNA from chromosome band 11q13; mutation of TP53; and loss of heterozygosity from chromosomes and chromosome arms 1, 3p, 6q, 7q, 8p, 11, 13q, 16q, 17, 18q, and 22q.
3	8605112	Recently, linkage analyses of large families with a predisposition to breast cancer have been performed in order to map breast cancer susceptibility genes (TP53, BRCA1, BRCA2).
4	8710380	The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation.
5	9005288	Mutations in BRCA1, BRCA2, p53, and the Cowden disease gene are relatively uncommon, are highly penetrant, and produce striking familial clusters of breast cancer.
6	9005288	BRCA1 and BRCA2 are the most important of these, accounting for an estimated 80% of hereditary breast cancer and 5 to 6% of all breast cancers.
7	9005288	Specific BRCA1 and BRCA2 mutations are of particular importance in population subgroups, such as those identified among Jewish women of central European (Ashkenazi) origin.
8	9090474	Other genes associated with inherited susceptibility to ovarian cancer include BRCA2, p53, and the DNA mismatch repair genes.
9	9164266	Three genes have now been identified that confer increased susceptibility in families with a clear hereditary (i.e., Mendelian) pattern of expression: BRCA1, BRCA2 and p53.
10	9164266	Some evidence is available to implicate three additional genes that fit this category: AT, ESR and HRAS1.
11	9171368	Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos.
12	9171368	Mutations of the human BRCA1 and BRCA2 genes encoding tumor suppressors have been implicated in inherited predisposition to breast and other cancers.
13	9171368	Disruption of the homologous mouse genes Brca1 and Brca2 by targeting showed that they both have indispensable roles during embryogenesis, because nullizygous embryos become developmentally retarded and disorganized, and die early in development.
14	9171368	In Brca1 mutants, the onset of abnormalities is earlier by one day and their phenotypic features and time of death are highly variable, whereas the phenotype of Brca2 null embryos is more uniform, and they all survive for at least 8.5 embryonic days.
15	9171368	Observations with Brca1/Brca2 double nullizygotes raise the possibility that the two developmental pathways could be linked.
16	9171368	Interestingly, the impact of the Brca1 or Brca2 null mutation is less severe in a p53 null background.
17	9212093	Double indemnity: p53, BRCA and cancer. p53 mutation partially rescues developmental arrest in Brca1 and Brca2 null mice, suggesting a role for familial breast cancer genes in DNA damage repair.
18	9221812	Genomic deletions in the BRCA1, BRCA2 and TP53 regions associate with low expression of the estrogen receptor in sporadic breast carcinoma.
19	9221812	In the present study we analyzed 266 spontaneously arising breast carcinomas for allelic losses in the BRCA1 and TP53 regions on chromosome 17, the BRCA2 region on chromosome 13, the ATM (mutated in ataxia-telangiectasia) region on chromosome 11 and on the chromosomal arms 7q and 16q.
20	9221812	The analysis of genetic and clinical observations revealed significant associations: absence of expression of the estrogen receptor was linked to a high rate of allelic losses of markers in the BRCA1, TP53 and BRCA2 regions.
21	9221812	Our data point to a relationship between clinically relevant prognostic factors and specific genomic deletions in the BRCA1, BRCA2 and TP53 region.
22	9408754	Allelic loss at BRCA1, BRCA2, and adjacent loci in relation to TP53 abnormality in breast cancer.
23	9408754	Tumors from 90 patients were examined for TP53 abnormality and loss of heterozygosity (LOH) at 11 loci on 17q (17q11.2-21) and 13q (13q12-14), including the loci for BRCA1 and BRCA2.
24	9408754	The increased LOH in relation to TP53 abnormality was statistically significant at the BRCA1, D17S588, and D13S267 loci (P < 0.05) but not at the locus for BRCA2 (P = 0.64).
25	9421204	The prevalence of abnormal BRCA1, BRCA2, and p53 genes. c.
26	9467939	Breast tumours from BRCA1 and BRCA2 mutation carriers are genetically instable and display specific patterns of chromosomal aberrations, suggestive of distinct genetic pathways in tumour progression.
27	9467939	The frequency of abnormalities affecting chromosome 17p and the TP53 gene was determined in 27 breast tumours from 26 female patients carrying the Icelandic BRCA2 founder mutation (999del5).
28	9509273	Within the past few years, a number of genes associated with a high risk of breast cancer have been identified, including BRCA1, BRCA2, p53, and the Cowden disease gene PTEN/MMAC1.
29	9509273	These genes appear to function as tumor suppressors, and although their mutation frequency in the general population is low, certain populations have a carrier frequency of up to 1% for particular BRCA1 and BRCA2 mutations.
30	9619832	Regulation of BRCA1 and BRCA2 expression in human breast cancer cells by DNA-damaging agents.
31	9619832	Germline mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 have been linked to the development of breast cancer, ovarian cancer, and other malignancies.
32	9619832	Recent studies suggest that the BRCA1 and BRCA2 gene products may function in the sensing and/or repair of DNA damage.
33	9619832	To investigate this possibility, we determined the effects of various DNA-damaging agents and other cytotoxic agents on the mRNA levels of BRCA1 and BRCA2 in the MCF-7 and other human breast cancer cell lines.
34	9619832	We found that several agents, including adriamycin (a DNA intercalator and inhibitor of topoisomerase II), camptothecin (a topoisomerase I inhibitor), and ultraviolet radiation induced significant decreases in BRCA1 and BRCA2 mRNA levels.
35	9619832	Decreased levels of BRCA1 and BRCA2 mRNAs were observed within 6-12 h after treatment with adriamycin and persisted for at least 72 h.
36	9619832	U.V. radiation induced dose-dependent down-regulation of BRCA1 and BRCA2 mRNAs, with significant decreases in both mRNAs at doses as low as 2.5 J/m2, a dose that yielded very little cytotoxicity.
37	9619832	Adriamycin-induced down-regulation of BRCA1 and BRCA2 mRNAs was first observed at doses that yielded relatively little cytotoxicity and little or no apoptotic DNA fragmentation.
38	9619832	Adriamycin and U.V. radiation induced distinct dose- and time-dependent alterations in the cell cycle distribution; but these alterations did not correlate well with corresponding changes in BRCA1 and BRCA2 mRNA levels.
39	9619832	However, the adriamycin-induced reduction in BRCA1 and BRCA2 mRNA levels was correlated with p53 functional status.
40	9619832	MCF-7 cells transfected with a dominant negative mutant p53 (143 val-->ala) required at least tenfold higher doses of adriamycin to down-regulate BRCA1 and BRCA2 mRNAs than did parental MCF-7 cells or control-transfected MCF-7 clones.
41	9619832	These results suggest that BRCA1 and BRCA2 may play roles in the cellular response to DNA-damaging agents and that there may be a p53-sensitive component to the regulation of BRCA1 and BRCA2 mRNA expression.
42	9679765	Down-regulation of BRCA1 and BRCA2 in human ovarian cancer cells exposed to adriamycin and ultraviolet radiation.
43	9679765	Germ-line mutations of the BRCA1 and BRCA2 genes predispose women to develop cancers of the breast and ovary, but the biologic functions of these genes remains unclear.
44	9679765	We have investigated the responses of the BRCA1 and BRCA2 gene products to cytotoxic agents in 3 human ovarian cancer cell lines: SK-OV-3 (which contains a p53 deletion mutation), CAOV-3 (which over-expresses a mutant p53) and PA-1 (which expresses wild-type p53).
45	9679765	In screening studies, we determined the effects of 7 different agents on BRCA1 and BRCA2 expression.
46	9679765	We found that Adriamycin (ADR) and ultraviolet (UV)radiation significantly down-regulated BRCA1 and BRCA2 mRNA expression in SK-OV-3 cells.
47	9679765	On the other hand, camptothecin, nitrogen mustard, taxol, vincristine and etoposide had no effect on BRCA1 or BRCA2 mRNA levels at doses that yielded degrees of cytotoxicity similar to or greater than ADR.
48	9679765	The down-regulation of BRCA1 and BRCA2 mRNAs was dose and time dependent; significant down-regulation was first observed at 8-16 hr after exposure to ADR.
49	9679765	The ADR doses required for significant decreases of BRCA1 and BRCA2 were about 10-15, 5-10 and 2 microM, respectively, for SK-OV-3, CAOV-3 and PA-1; the IC50 doses for loss of cell viability (determined by Trypan blue dye exclusion) were 23, 14 and 0.4 microM, respectively.
50	9679765	Thus, at equitoxic doses of ADR, PA-1 cells were more resistant to down-regulation of BRCA1 and BRCA2 than SK-OV-3 or CAOV-3.
51	9679765	Our findings suggest that 1) BRCA1 and BRCA2 expression in human ovarian cancer cell lines is selectively down-regulated by 2 DNA-damaging agents (ADR and UV radiation); 2) these responses are not due to non-specific cytotoxicity; and 3) the BRCA1 and BRCA2 responses may be dependent, in part, on the p53 functional status of the cells.
52	9679765	We speculate that the down-regulation of BRCA1 and BRCA2 may be part of a cellular survival response activated by certain forms of DNA damage.
53	9796697	p53 mutation with frequent novel condons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours.
54	9796697	The status of p53 was investigated in breast tumours arising in germ-line carriers of mutant alleles of BRCA1 and BRCA2 and in a control series of sporadic breast tumours. p53 expression was detected in 20/26 (77%) BRCA1-, 10/22 (45%) BRCA2-associated and 25/72 (35%) grade-matched sporadic tumours.
55	9796697	Analysis of additional genes, p16INK4, Ki-ras and beta-globin revealed absence or very low incidence of mutations, suggesting that the higher frequency of p53 mutation in the BRCA-associated tumours does not reflect a generalized increase in susceptibility to the acquisition of somatic mutation.
56	9796697	Furthermore, absence of frameshift mutations in the polypurine tracts present in the coding sequence of the TGF beta type II receptor (TGF beta IIR) and Bax implies that loss of function of BRCA1 or BRCA2 does not confer a mutator phenotype such as that found in tumours with microsatellite instability (MSI). p21Waf1 was expressed in BRCA-associated tumours regardless of p53 status and, furthermore, some tumours expressing wild-type p53 did not express detectable p21Waf1.
57	9832031	To date, only a small number of tumour suppressor genes, including BRCA1, BRCA2, and p53, have been associated with familial breast or breast/ovarian cancer families.
58	9973246	We review many of the molecular events important in the pathogenesis of breast cancer, including inherited abnormalities in BRCA-1 and BRCA-2, p53, ATM, and PTEN and sporadic alterations in growth factors and their receptors, signal transduction, cell cycle control, DNA repair, cell death, angiogenesis, and invasion and metastasis.
59	10030809	Recent advances in molecular biology, however, have shown that hereditary breast cancer may eventuate as a result of mutations on several specific gene loci including BRCA1, BRCA2, ATM gene, PTEN and p53.
60	10030809	Several other less frequently occurring predisposition genes such as the androgen receptor gene (AR), the HNPCC genes and the oestrogen receptor gene may also be involved, but to a lesser extent.
61	10030809	Overall, approximately 5-10% of all breast cancers are thought to involve one of these inherited predisposition genes, with BRCA1 and BRCA2 being responsible for as much as 90% of this group.
62	10066082	Possible molecular prognostic markers are: BRCA-1, BRCA-2, p53, erbB oncogenes, loss of heterozygosity (LOH), chromosomal aberrations, microsatellite instability, transforming growth factor alpha (TGFalpha), and the multiple drug resistance (MDR) gene.
63	10195418	The function of BRCA1 has been examined in gene knockout mice in which the nullizygous mice die early in utero, but this lethality can be partially rescued by a nullizygous p53 mutation.
64	10195418	Wild-type BRCA1 protein binds to a number of cellular proteins, including DNA repair protein Rad51, tumor suppressor p53, RNA polymerase II holoenzyme, RNA helicase A, CtBP-interacting protein, c-myc, BRCA1-associated RING domain protein (BARD1), BRCA2 protein, etc.
65	10213514	Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study.
66	10213514	Breast cancers arising in women with and without a germline mutation in the BRCA1 or BRCA2 gene display different histological features, which suggests unique mechanisms of molecular pathogenesis: We used a molecular pathological analysis to define the genetic abnormalities relevant to these specific pathogeneses.
67	10213514	Tumor material was studied from 40 women with breast cancer diagnosed before 40 years of age, sampled from a population-based study and stratified by BRCA1 and BRCA2 germline mutation status.
68	10213514	Breast cancers occurring in BRCA1 mutation carriers had significantly higher levels of p53 expression, including the preinvasive (carcinoma in situ) stage of disease, compared with cancers occurring in BRCA2 mutation carriers or women with no detectable germline mutation.
69	10213514	Expression of the prognostic factors c-erbB-2, cyclin D1, and estrogen receptor was significantly less common in BRCA1 mutation carriers.
70	10213514	Lower levels of cyclin D1 were also found in cancers from BRCA2 mutation carriers compared with non-mutation carriers.
71	10213514	Direct p53 mutation analysis revealed mutations in 18% of all of the early-onset breast cancers within the study and included rare insertion and deletional mutations in cancers from BRCA1 mutation carriers.
72	10213514	Our data indicate that a BRCA1 breast cancer phenotype may be recognized by an exceptionally high proliferation rate and early and frequent p53 overexpression but infrequent selection for overexpression of several other prognostic factor proteins known to be involved in breast oncogenesis.
73	10229196	Inheritance of germ-line mutant alleles of BRCA1 and BRCA2 confers a markedly increased risk of breast cancer and we have previously reported a higher incidence of p53 mutations in these tumours than in grade matched sporadic tumours.
74	10229196	The rarity of these mutants in human cancer and their multiple occurrence in BRCA-associated breast tumours suggests that these novel p53 mutants are selected during malignant progression in the unique genetic background of BRCA1- and BRCA2-associated tumours.
75	10333246	However, a mutation in a tumor suppressor gene, such as p53, BRCA1, BRCA2, or ATM, has been determined to be one mechanism of breast carcinogenesis.
76	10333246	It has been established that inherited mutations in p53, BRCA1, and BRCA2 significantly contribute to breast cancer risk, although the importance of an inherited ATM mutation is controversial.
77	10333246	In this article, we review the relevancy of p53, BRCA1, BRCA2, and ATM mutations to breast cancer development, and review the in vitro, in vivo, and clinical data exploring the mechanisms by which these mutations affect genomic integrity and DNA damage repair.