Localization of a Breast Cancer Susceptibility Gene, <i>BRCA2</i> , to Chromosome 13q12-13
SciencePublished 30 September 1994
Richard Wooster, Susan L. Neuhausen, Jonathan Mangion, Yvette Quirk, Deborah Ford, Nadine Collins
Citations1,896
SJR quartileQ1
SJR score10.42
SNIP6.62
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13, which preliminary evidence suggests suggests confers a high risk of breast cancer but does not confer a substantially elevated risk of ovarian cancer.
Abstract
A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.
Keywords
Biochemistry, Genetics and Molecular Biology
ScienceGerm Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms
3,778 Citations1990David Malkin, Frederick P. Li +9 more
Germ line p53 mutations have been detected in all five LFS families analyzed and can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.
Proceedings of the National Academy of SciencesStrategies for multilocus linkage analysis in humans.
2,574 Citations1984G.M. Lathrop, J.-M. Lalouel +2 more
The results show that considerable economy and efficiency can be brought to the mapping endeavor by resorting to appropriate strategies of detecting linkage and by constructing the human genetic map on a common reference panel of families.
ScienceLinkage of Early-Onset Familial Breast Cancer to Chromosome 17q21
2,541 Citations1990Jeff Hall, Ming K. Lee +5 more
Ch Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease, and genetic analysis yields a lod score of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-ONSet families and negative lod scores in familiesWith late-onsets disease.
Nature GeneticsThe 1993–94 Généthon human genetic linkage map
1,852 Citations1994Gàbor Gyapay, Jean Morissette +8 more
A new genetic linkage map containing a total of 2,066 (AC)n short tandem repeats, 60% of which show a heterozygosity of over 0.7 is presented.
NatureA second-generation linkage map of the human genome
1,697 Citations1992Jean Weissenbach, Gàbor Gyapay +6 more
A linkage map of the human genome has been constructed based on the segregation analysis of 814 newly characterized polymorphic loci containing short tracts of (C-A)n repeats in a panel of DNAs from eight large families.
PubMedFaster sequential genetic linkage computations.
1,373 Citations1993Robert W. Cottingham, Ramana M. Idury +1 more
A variety of algorithmic improvements are described, which synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.
PubMedGenetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium.
1,253 Citations1993Douglas F. Easton, D. Timothy Bishop +2 more
The results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist.
NatureGerm-line transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome
1,217 Citations1990Shiv Srivastava, Zhiqiang Zou +3 more
The p53 gene in a family affected by Li–Fraumeni syndrome, a rare autosomal dominant syndrome characterized by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites, had the same point mutation in codon 245 (GGC→GAC), which leads to substitution of aspartic acid for glycine in one of the regions identified as a frequent target of point mutations in p53.
New England Journal of MedicineIncidence of Cancer in 161 Families Affected by Ataxia–Telangiectasia
947 Citations1991Michael Swift, Daphne Morrell +2 more
Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene, which predisposes heterozygotes to cancer, particularly breast cancer in women.
ScienceInactivation of the Retinoblastoma Susceptibility Gene in Human Breast Cancers
596 Citations1988Eva Y.-H.P. Lee, Hoang To +4 more
The retinoblastoma susceptibility gene is shown to be inactivated in two of nine human breast cancer cell lines examined, significant in relation to proposed genetic mechanisms of breast cancer formation.
ScienceAssignment of a Locus for Familial Melanoma, MLM, to Chromosome 9p13-p22
526 Citations1992Lisa Cannon‐Albright, David E. Goldgar +14 more
Linkage analysis of Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22, previously implicated in homozygous deletions in melanoma tumors.
The LancetFamilial breast-ovarian cancer locus on chromosome 17q12-q23
518 Citations1991G M Lenoir
Findings suggest that the chromosomal region 17q12-q23, previously shown to contain a gene for early-onset breast cancer, is also associated with a proportion of hereditary ovarian cancers.
ScienceStructural Rearrangement of the Retinoblastoma Gene in Human Breast Carcinoma
411 Citations1988Anne Tang, Jennifer M. Varley +3 more
The results further support the concept that the human RB1 gene has pleiotropic effects on specific types of cancer.
Nature GeneticsInstability of short tandem repeats (microsatellites) in human cancers
410 Citations1994Richard Wooster, A.M. Cleton-Jansen +11 more
The allele sizes of polymorphic microsatellite repeats in DNA from human cancers were compared to normal DNA from the same patients and evidence of an extra allele of a different size in the tumour which was not present in the normal DNA was found.
Nature GeneticsA germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome
251 Citations1992Richard Wooster, Jonathan Mangion +8 more
A family in which two brothers who both developed breast cancer had clinical and endocrinological evidence of androgen resistance is reported, the first report of a germline mutation in a member of the steroid/thyroid hormone receptor superfamily associated with the development of cancer.
Proceedings of the National Academy of SciencesLoss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13.
201 Citations1987C Lundberg, Lambert Skoog +2 more
GenomicsAt least four different chromosomal regions are involved in loss of heterozygosity in human breast carcinoma
195 Citations1989Peter Devilee, Marianne van den Broek +5 more
The results suggest that some of the observed allele losses reflect random events, possibly as a result of genetic instability, but are not without biological significance for the progression of particular subclasses of breast tumors.
GenomicsComplete Genomic Sequence of the Human Retinoblastoma Susceptibility Gene
167 Citations1993Junya Toguchida, Terri L. McGee +5 more
A 180,388-bp contig encompassing the human retinoblastoma gene was sequenced in its entirety, revealing a high (A+T)/(G+C) ratio and a high density of Line-1 (L1) repeat sequences, which should enhance studies of this locus and of the organization of the human genome.
Nature GeneticsFamilial male breast cancer is not linked to the BRCA1 locus on chromosome 17q
157 Citations1994Michael R. Stratton, Deborah Ford +15 more
There is a gene(s) other than BRCA1 which predisposes to early–onset breast cancer in women and which confers a higher risk of male breast cancer, and identification of additional pedigrees that include cases ofmale breast cancer may facilitate the mapping and isolation of this gene.
PubMedLoss of heterozygosity and p53 gene mutations in breast cancer.
124 Citations1994Guoren Deng, L C Chen +6 more
There was no association between p53 mutations and LOH at 17p (site of the p53 gene), suggesting that breast cancers often have only one defective allele of thep53 gene.
British Journal of CancerMutations in p53 do not account for heritable breast cancer: a study in five affected families
75 Citations1991J. Prosser, PA Elder +4 more
Genetic EpidemiologySegregation and linkage analysis of nine Utah breast cancer pedigrees
68 Citations1988D. Timothy Bishop, Lisa Cannon‐Albright +4 more
The analysis of nine Utah families that were ascertained for clusters of breast cancer cases shows the inherent difficulty of obtaining parameter estimates for segregation analysis when families are ascertained from a cluster of cases.
PubMedClose physical linkage of the FLT1 and FLT3 genes on chromosome 13 in man and chromosome 5 in mouse.
67 Citations1993Olivier Rosnet, Dennis A. Stephenson +5 more
A third cluster located on chromosome 13q and containing two contiguous RTK genes, FLT1 and FLT3 are defined, which appears to lie within a 350 kb Mlu I fragment, on mouse chromosome 5.
Human GeneticsAbsence of linkage to the ataxia telangiectasia locus in familial breast cancer
58 Citations1993Richard Wooster, Deborah Ford +5 more
It is concluded that the contribution of AT to familial breast cancer is likely to be minimal and typed five markers on chromosome 11q in 16 breast cancer families found no evidence for linkage between breast cancer and chromosomes 11q markers.
Proceedings of the National Academy of SciencesFte-1, a v-fos transformation effector gene, encodes the mammalian homologue of a yeast gene involved in protein import into mitochondria.
57 Citations1992C J Kho, Helmut Zarbl
Results demonstrate that the mammalian homologue of a gene implicated in protein import into yeast mitochondria is a v-fos transformation effector gene.
PubMedNo evidence for germline mutations in exons 5-9 of the p53 gene in 25 breast cancer families.
52 Citations1992William Warren, Rosalind A. Eeles +8 more
The results of this study indicate that familial breast cancer does not usually result from germline point mutations in the p53 gene.