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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of genes are known to be involved in inherited susceptibility to breast and/or ovarian cancer. In the context of high-risk families the most important genes are BRCA1 on chromosome 17q, which is associated with a high penetrance of both breast and ovarian cancer, and BRCA2 on chromosome 13q, which causes a high risk of breast cancer but a lower risk of ovarian cancer. Other high-risk cancer genes that confer increased risks of breast or ovarian cancer in addition to other cancers include the hereditary non-polyposis colorectal cancer genes and the TP53 gene, which causes breast cancer as part of the Li-Fraumeni syndrome. The predisposing mutations in these genes are relatively rare in the population. More common genes which are associated with an increased, but lower, risk of breast cancer are the ataxiatelangiectasia gene and the HRAS1 gene. This paper reviews recent progress in mapping and cloning of these susceptibility genes, and provides estimates of the cancer risks associated with each gene and the frequency of predisposing mutations.
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PMID:The genetics of breast and ovarian cancer. 754 24

Loss of heterozygosity (LOH) at loci from chromosome 13 is frequently observed in breast cancer. Chromosome 13 contains at least two cancer genes, the well-characterized RB1 gene located at 13q14 and the breast cancer-susceptibility gene, BRCA2, recently localized to 13q12. To investigate the possible involvement of BRCA2 in sporadic breast tumors, we looked at LOH at eight microsatellite (CA)n markers distributed along chromosome 13 in a panel of 59 primary breast carcinomas. We show that some LOH does not include the RB1 locus and is associated with the BRCA2 gene region.
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PMID:Patterns of loss of heterozygosity at loci from chromosome arm 13q suggests a possible involvement of BRCA2 in sporadic breast tumors. 754 38

We identified a homozygous deletion in a pancreatic carcinoma (DPC) that localized to a 1-cM region at chromosome 13q12.3, which lay within the 6-cM locus of familial breast cancer susceptibility (BRCA-2). Here we present a physical map of the region, consisting of YAC, PAC, and cosmid contigs. The YAC contig comprises 16 clones that together span the entire BRCA2 region. The PAC contig comprises 22 clones that together span the DPC region. Seventy cosmid clones were localized within and near the DPC region. Thirty-five sequence-tagged sites were defined and localized within the map. The map indicates the size of the DPC region to be near 250 kb, and provides mapped and cloned resources for the search for the putative tumor suppressor gene(s) in the region.
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PMID:An integrated high-resolution physical map of the DPC/BRCA2 region at chromosome 13q12. 755 31

Because of a family history of breast cancer, a 51-year-old patient underwent bilateral subcutaneous mammectomy in 1988. In February 1994 she presented with a nodule in the supramedial quadrant on the left. Needle biopsy suggested galactophoric adenocarcinoma which was confirmed histologically. A 1.5 cm tumour was removed together with a 3 cm reliquat of glandular tissue. Twelve axillary nodes were dissected and were found to be free of neoplastic infiltration. Hormone receptors were positive. Post-operative radiotherapy was performed. The outcome is unchanged at 6 months. Bilateral subcutaneous mammectomy can be proposed as a preventive measure in patients at risk, but as demonstrated by this case, exeresis is usually incomplete. The level of protection actually achieved is thus questionable. Clinicians should be aware of the risk of breast cancer developing after such elective operations since early screening programmes and the development of genetic methods based on the search for BRCA1 and BRCA2 genes will undoubtedly increase the number of patients requesting preventive measures.
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PMID:[Breast cancer after preventive subcutaneous mastectomy]. 756 34

There is now unequivocal evidence that an estimated 5% of breast cancer cases is inherited in families. Inherited predisposition of cancer in these families is thought to be the result of a mutation in one of several highly penetrant autosomal dominant genes such as BRCA1 or BRCA2. The BRCA1 gene which is localized on chromosome 17 q was recently isolated and at about the same time BRCA2 was localized to chromosome 13 q. A number of other genetic mutations is also associated with predisposition to breast cancer but accounts for a very small proportion of inherited breast cancer. Many women want to know whether they have inherited a gene predisposing to breast cancer. Those with a family history of breast cancer are particularly concerned about their risk of disease. Currently the assessment of an individual's risk of breast cancer can be undertaken using prediction models based on family history and can be further refined when molecular genetic investigations became available. Without molecular characterisation the Claus tables derived from the Cancer and Steroid Hormone Study data set are best suited to predict breast cancer risk based on age of onset of affected relatives. Direct screening for mutations in breast cancer genes in not yet generally available. Testing for inherited susceptibility is currently being offered to selected families where multiple cases of breast and/or ovarian cancer are diagnosed at an early age (younger than 45 years) as part of research protocols. In these families the so-called indirect gene analysis for linkage of disease to BRCA1 and BRCA2 or the direct analysis of mutations with functional significance in the BRCA1 gene allows relatively refined risk assessment for non-diseased female family members. Some examples will be presented to illustrate risk assessment in different familial and individual situations. Risk assessment including test result interpretation and counselling can be appropriately provided directly to the patient by physicians and genetic counsellors in a coordinated genetic counselling setting.
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PMID:[Risk assessment for familial occurrence of breast cancer]. 757 5

Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of breast tumours. This may reflect the inactivation of the retinoblastoma susceptibility gene RB1. However, recently another candidate tumour-suppressor gene has been identified on chromosome 13 by linkage analysis, the breast cancer susceptibility gene BRCA2. To investigate the involvement of BRCA2 in sporadic breast cancer 200 breast tumours were tested for LOH on chromosome band 13q12-q14, using 11 highly polymorphic microsatellite markers. LOH was found in 65 tumours, which all showed simultaneously loss of BRCA2 and RB1. Of 12 breast tumour cell lines tested with polymorphic microsatellite markers, seven showed a contiguous region of homozygosity on 13q12-q14, suggesting LOH in the tumour from which the cell line had been derived. One cell line showed homozygosity in the BRCA2 region and heterozygosity at RB1. This is the only indication that BRCA2 is a distinct target for LOH on chromosome 13 in addition to RB1.
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PMID:Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13. 757 75

In this study we examined loss of heterozygosity (LOH) on chromosome 13q12-13 in 50 tumors from BRCA2 carriers in five families showing strong evidence of linkage to BRCA2. In addition to high frequency of LOH in female breast cancer, LOH was observed in tumors of the prostate, ovary, cervix, colon, male breast, and ureter. All detected losses involved the wild-type chromosome. These results suggest that BRCA2 is a tumor suppressor gene and may be involved in the tumorigenesis of several cancer types in addition to breast cancer.
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PMID:Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13. 758 15

Homozygous deletions have been central to the discovery of several tumor-suppressor genes, but their finding has often been either serendipitous or the result of a directed search. A recently described technique [Lisitsyn, N., Lisitsyn, N. & Wigler, M. (1993) Science 259, 946-951] held out the potential to efficiently discover such events in an unbiased manner. Here we present the application of the representational difference analysis (RDA) to the study of cancer. We cloned two DNA fragments that identified a homozygous deletion in a human pancreatic adenocarcinoma, mapping to a 1-centimorgan region at chromosome 13q12.3 flanked by the markers D13S171 and D13S260. Interestingly, this lies within the 6-centimorgan region recently identified as the BRCA2 locus of heritable breast cancer susceptibility. This suggests that the same gene may be involved in multiple tumor types and that its function is that of a tumor suppressor rather than that of a dominant oncogene.
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PMID:Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. 759 59

Reactive oxygen species and free radicals that are produced during normal metabolism can potentially damage cellular macromolecules. Defenses against such damage include a number of antioxidant enzymes that specifically target the removal or dismutation of the reactive agent. We report here the isolation and regional mapping of a human gene, TDPX1, that encodes an enzyme homologous to a yeast thioredoxin-dependent peroxide reductase (thioredoxin peroxidase, TPX). The human TDPX1 coding sequence was determined from the product of a polymerase chain reaction (PCR) amplification of human cDNA. Based on PCR analysis of DNA from a human/rodent somatic cell hybrid panel, the TDPX1 locus was assigned to chromosome 13. Further localization of the locus to 13q12 was accomplished by fluorescence in situ hybridization analysis, using as a probe DNA from a yeast artificial chromosome (YAC) that contains the TDPX1 gene. It was also determined by PCR analysis of various YACs that the TDPX1 locus is in the region of the dinucleotide repeat markers D13S289 and D13S290. This regional mapping localizes the TDPX1 gene to a genomic region recently shown to contain the breast cancer susceptibility gene BRCA2 and a gene associated with a form of muscular dystrophy. Oxygen radical metabolism has been hypothesized to be important for cancer, muscular dystrophy, and other disorders, so TDPX1 should be considered a candidate gene for these diseases.
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PMID:Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent peroxide reductase gene (TPX), to chromosome 13q12. 760 88

Breast cancer is rare in men, and family history of the disease is a risk factor. The recently discovered BRCA2 gene on chromosome 13q is thought to account for some families with increased risk of breast cancer, including male breast cancer. We describe a family with multiple cases of male breast cancer but, interestingly, no increase in female breast cancer. Linkage to the BRCA2 region is demonstrated and all the affected men share the same haplotype for the BCRA2 markers and loss of the other alleles in their tumours.
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PMID:Linkage to BRCA2 region in hereditary male breast cancer. 765 81


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