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

A genetic linkage map of human chromosome 21 has been constructed using 22 anonymous DNA markers and five complementary DNAs (cDNAs) encoding the amyloid beta protein precursor (APP), superoxide dismutase 1 (SOD1), the ets-2 proto-oncogene (ETS2), the estrogen inducible breast cancer locus (BCEI), and the leukocyte antigen, CD18 (CD18). Segregation of RFLPs detected by these DNA markers was traced in the Venezuelan Reference Pedigree (VRP). A comprehensive genetic linkage map consisting of the 27 DNA markers spans 102 cM on the long arm of chromosome 21. We have confirmed our initial findings of a dramatically increased rate of recombination at the telomere in both females and males and of significantly higher recombination in females in the pericentromeric region. By comparing patterns of recombination in specific regions of chromosome 21 with regard to both parental sex and age, we have now identified a statistically significant downward trend in the frequency of crossovers in the most telomeric portion of chromosome 21 with increasing maternal age. A less significant decrease in recombination with increasing maternal age was observed in the pericentromeric region of the chromosome. These results may help in ultimately understanding the physical relationship between recombination and nondisjunction in the occurrence of trisomy 21.
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PMID:A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age. 134 93

Band q13 of chromosome 11 is frequently amplified in human breast cancers, but the gene(s) responsible for the emergence of this amplicon remain(s) elusive as yet. As a tribute to the complexity of the amplification events involving 11q13 sequences in human breast cancer, we have now studied a more telomeric region at 11q13.5-q14 defined by a new transcription unit, D11S833E. We have observed that amplicons present in cell lines and primary tumors amplified for both BCL1 and D11S833E could be interrupted between these two loci. Such discontinuities were demonstrated by using a probe for the KRN1 gene, which we have localized between the BCL1/FGF4 region and D11S833E. In fact, KRN1 was not present in 4 out of 10 amplicons bearing both BCL1 and D11S833E. Furthermore, we have observed tumors in which D11S833E could be amplified in the absence of amplification of other known markers of 11q13. Therefore, D11S833E defines a new and independent amplification unit in this region.
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PMID:DNA amplification at 11q13.5-q14 in human breast cancer. 146 54

Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed.
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PMID:Familial breast cancer. 151 Nov 56

In the course of our study on the amplification of 11q13 sequences in human breast cancer, we have investigated the amplification status of the anonymous DNA fragment D11S97 in a series of 125 mammary tumors. Our results indicate that, as with bladder carcinomas, D11S97 can be amplified separately from BCL1. In addition, we have shown that D11597 is physically linked to both D11S146 and BCL1, and is less than 100 kb centromeric to the D115146. These results indicate that, in addition to other 11q13 loci, sequences located approximately 500 kb centromeric from BCL1 could contribute to carcinogenesis of epithelial cells in vivo.
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PMID:Amplification of 11q13 DNA sequences in human breast cancer: D11S97 identifies a region tightly linked to BCL1 which can be amplified separately. 156 70

The DNA of paired tumour and blood leucocyte samples from a large series of breast cancer patients was analysed to map regions of loss of heterozygosity on chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed, and a third of informative tumours had also lost an allele at the long arm locus THH59. On the short arm two distinct regions of loss of heterozygosity were identified, in bands p13-3 and p13-1. The latter probably involves the structural gene p53, which has been implicated as an oncogene or as a tumour suppressor in various human cancers. 17p 13-3, however, showed a significantly higher frequency of loss of heterozygosity, and there was no correlation between allele losses at the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated with overexpression of p53 mRNA, suggesting the existence of a gene some 20 megabases telomeric of p53 that regulates its expression. Lesions of this regulatory gene seem to be involved in the majority of breast cancers.
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PMID:Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. 197 43

In this study, we analyzed 105 paired sporadic primary breast tumor and normal tissue samples for loss of heterozygosity (LOH) on chromosome 17, using 12 polymorphic markers. We have identified partial or interstitial LOH in five separate regions of chromosome 17. Two of the deleted regions lie on the short arm of the chromosome, the first (region I, D17S5) in the telomeric part, distal to TP53 and the second spanning the TP53 gene (region II). Three of the five deleted regions lie on the long arm of chromosome 17: region III, on the proximal long arm between D17S250 and THRA1; region IV, between D17S776 and D17S579, including the BRCA1 gene, and region V, located distal to D17S733. No statistically significant correlations were observed between clinicopathological characteristics or steroid hormone receptor status and deletion of either region I or II. However, patients whose tumors had LOH for region I showed relapse or death more frequently than patients with tumors informative for this region but without LOH (p = 0.002). Statistically significant correlations between LOH at each of the three deleted regions of 17q and a high mitotic index were observed (region III, p = 0.005; region IV, p = 0.02, and region V, p = 0.004). In addition, LOH at region IV showed a significant association with paucity of estrogen receptors (p = 0.01). Our results show a complex pattern of LOH on chromosome 17 in breast cancer and a correlation of these events with different clinical parameters. This pattern suggests that particular subsets of allele loss may contribute specifically to different clinically defined subsets of sporadic breast tumors.
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PMID:Five distinct deleted regions on chromosome 17 defining different subsets of human primary breast tumors. 747 29

We have previously described a common region of deletion and allele loss on chromosome 17q in sporadic breast cancers that is likely to contain a tumor suppressor gene. The region, mapped to 17q12-q21, was bordered by D17S250 and D17S579 on the centromeric and telomeric sides, respectively. This deletion region overlaps the BRCA1 locus, which predisposes to familial breast and ovarian cancer. The most frequent loss of heterozygosity was observed at the thyroid hormone receptor alpha (THRA1) locus. Southern analysis revealed a rearrangement of THRA1 in the BT474 breast cancer cell line. This rearrangement represented a deletion of exons 8-10 of one THRA1 allele that was also coamplified with ERBB2. Northern blots showed two mutant transcripts in BT474 cells. Analysis of the mutant transcripts revealed fusion of the THRA1 exon 7 by splicing to a novel sequence designated BTR for "BT474 transcribed rearrangement." BTR was found to be highly conserved and mapped to 17q. The deletion in BT474 cells spans the entire BRCA1 region. To search for additional mutations in the THRA1 gene, all nine protein-encoding exons of THRA1 were examined for point mutations via single strand conformation analysis in a series of primary breast tumors, breast cancer cell lines, and lymphoblastoid cell lines derived from the youngest affected members of several German breast cancer families. No point mutations were detected, including the unrearranged THRA1 allele in BT474. We have thus excluded THRA1 as a commonly mutated sporadic breast cancer tumor suppressor gene and as the BRCA1 gene.
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PMID:Mutation analysis of the THRA1 gene in breast cancer: deletion/fusion of the gene to a novel sequence on 17q in the BT474 cell line. 751 Oct 52

A breast-ovarian cancer susceptibility gene, BRCA1, which is responsible for disease in approximately 45% of breast cancer families and most families that contain breast and ovarian cancer, has been assigned by genetic linkage to 17q12-21. Here, we report the analysis of three marker-disease recombinants in families that contain breast and ovarian cancer, two of which strongly suggest a location for BRCA1 telomeric to D17S702, a microsatellite polymorphism, and a third which suggests a location centromeric to EDH17B, the gene encoding estradiol-17B dehydrogenase. If the interpretation of these recombinants is correct, the results localise BRCA1 to an interval of < or = 1 cM.
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PMID:Localisation of the breast-ovarian cancer susceptibility gene (BRCA1) on 17q12-21 to an interval of < or = 1 cM. 751 78

Linkage studies have indicated that a gene on chromosome arm 17q, designated BRCA1, confers susceptibility to familial breast and ovarian cancer. To investigate the possible involvement of the BRCA1 gene in sporadic breast cancer we have analysed loss of heterozygosity (LOH) in a panel of 100 sporadic primary breast tumours using 10 PCR-based polymorphic markers from 17q12-21. Allele losses were detected in 40 of 100 tumours informative for at least one of the markers analysed. Of these 40 deleted tumours, 27 showed partial or interstitial loss on 17q. The pattern of LOH in the tumours with partial or interstitial LOH revealed three putative distinct deleted regions on 17q12-21. The first lies on the proximal long arm between D17S250 and THRA1; the second one lies between D17S776 and D17S579, the region containing the BRCA1 gene; and the third is telomeric to D17S733. The most frequently deleted region overlaps with the minimal region containing the BRCA1 gene, suggesting that this gene might also be associated with the development or progression of a proportion of sporadic breast tumours.
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PMID:Detailed deletion mapping of chromosome segment 17q12-21 in sporadic breast tumours. 752 47

Eight Icelandic breast cancer kindreds were subjected to linkage analyses with respect to 28 microsatellite loci dispersed along the short arm of chromosome 3. Breast tumors derived from these kindreds were concurrently scored for allelic imbalance with ten of the markers. Linkage to most markers could be excluded on the basis of negative LOD scores and haplotype analyses, although some moderately positive LOD scores resulted. A high frequency of imbalance in the familial tumors was seen with two of the markers in comparison with results obtained from sporadic material. The highest frequency (68%) of imbalance was detected with the marker D3S1217, which is located on 3p14.2-p14.1. Imbalance at the D3S1211 locus, which is more telomeric (3p24.2-p22), was not significantly elevated in the familial tumors. We suggest that the genetic defect responsible for breast cancer susceptibility in these families either promotes instability in the 3p14.2-p14.1 region or enhances the selective advantage of such changes.
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PMID:Linkage analysis and allelic imbalance in human breast cancer kindreds using microsatellite markers from the short arm of chromosome 3. 755 67


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