A population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland.

2.50
Hdl Handle:
http://hdl.handle.net/2336/49154
Title:
A population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland.
Authors:
Arason, A; Jonasdottir, A; Barkardottir, R B; Bergthorsson, J T; Teare, M D; Easton, D F; Egilsson, V
Citation:
J. Med. Genet. 1998, 35(6):446-9
Issue Date:
1-Jun-1998
Abstract:
The majority of breast cancer in high risk families is believed to result from a mutation in either of two genes named BRCA1 and BRCA2. A germline defect in either gene is usually followed by chromosomal deletion of the normal allele in the tumour. In Iceland two recurrent mutations have been identified, 999del5 BRCA2 and G5193A BRCA1. In this study, randomly selected pairs of sisters diagnosed with breast cancer at the age of 60 years or younger were analysed to evaluate the proportion of breast cancer resulting from BRCA1 and BRCA2. Genotypes and allele loss in tumour tissue from 42 sister pairs were compared using markers within and around the BRCA1 and BRCA2 genes. Eleven sister pairs were highly suggestive of BRCA2 linkage, and no obvious BRCA1 linkage was seen. Screening for the G5193A BRCA1 and 999del5 BRCA2 mutations showed the 999del5 mutation in the 11 BRCA2 suggestive pairs plus three pairs less indicative of linkage, and the G5193A BRCA1 mutation in one pair. When known mutation carriers are removed from the group, no indication of further linkage to BRCA1 or BRCA2 is seen. The results of our studies suggest that a large proportion of familial breast cancer in Iceland is the result of the 999del5 BRCA2 mutation, and it is unlikely that BRCA1 and BRCA2 germline mutations other than 999del5 and G5193A play a significant role in hereditary breast cancer in Iceland. Furthermore it can be concluded that most families with BRCA1 or BRCA2 linkage are easily identified by studying LOH around the defective gene in as few as two affected relatives.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://jmg.bmj.com/cgi/content/abstract/35/6/446

Full metadata record

DC FieldValue Language
dc.contributor.authorArason, A-
dc.contributor.authorJonasdottir, A-
dc.contributor.authorBarkardottir, R B-
dc.contributor.authorBergthorsson, J T-
dc.contributor.authorTeare, M D-
dc.contributor.authorEaston, D F-
dc.contributor.authorEgilsson, V-
dc.date.accessioned2009-02-16T09:42:58Z-
dc.date.accessioned2009-02-16T09:43:07Z-
dc.date.available2009-02-16T09:42:58Z-
dc.date.available2009-02-16T09:43:07Z-
dc.date.issued1998-06-01-
dc.date.submitted2009-02-16-
dc.identifier.citationJ. Med. Genet. 1998, 35(6):446-9en
dc.identifier.issn0022-2593-
dc.identifier.pmid9643283-
dc.identifier.doi10.1136/jmg.35.6.446-
dc.identifier.urihttp://hdl.handle.net/2336/49173-
dc.identifier.urihttp://hdl.handle.net/2336/49154-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractThe majority of breast cancer in high risk families is believed to result from a mutation in either of two genes named BRCA1 and BRCA2. A germline defect in either gene is usually followed by chromosomal deletion of the normal allele in the tumour. In Iceland two recurrent mutations have been identified, 999del5 BRCA2 and G5193A BRCA1. In this study, randomly selected pairs of sisters diagnosed with breast cancer at the age of 60 years or younger were analysed to evaluate the proportion of breast cancer resulting from BRCA1 and BRCA2. Genotypes and allele loss in tumour tissue from 42 sister pairs were compared using markers within and around the BRCA1 and BRCA2 genes. Eleven sister pairs were highly suggestive of BRCA2 linkage, and no obvious BRCA1 linkage was seen. Screening for the G5193A BRCA1 and 999del5 BRCA2 mutations showed the 999del5 mutation in the 11 BRCA2 suggestive pairs plus three pairs less indicative of linkage, and the G5193A BRCA1 mutation in one pair. When known mutation carriers are removed from the group, no indication of further linkage to BRCA1 or BRCA2 is seen. The results of our studies suggest that a large proportion of familial breast cancer in Iceland is the result of the 999del5 BRCA2 mutation, and it is unlikely that BRCA1 and BRCA2 germline mutations other than 999del5 and G5193A play a significant role in hereditary breast cancer in Iceland. Furthermore it can be concluded that most families with BRCA1 or BRCA2 linkage are easily identified by studying LOH around the defective gene in as few as two affected relatives.en
dc.language.isoenen
dc.publisherBritish Medical Associationen
dc.relation.urlhttp://jmg.bmj.com/cgi/content/abstract/35/6/446en
dc.subject.meshAge Factorsen
dc.subject.meshBRCA1 Proteinen
dc.subject.meshBRCA2 Proteinen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshFemaleen
dc.subject.meshGene Deletionen
dc.subject.meshGenes, BRCA1en
dc.subject.meshGenetic Markersen
dc.subject.meshHeterozygote Detectionen
dc.subject.meshHumansen
dc.subject.meshMiddle Ageden
dc.subject.meshMutationen
dc.subject.meshNeoplasm Proteinsen
dc.subject.meshNuclear Familyen
dc.subject.meshPoint Mutationen
dc.subject.meshTranscription Factorsen
dc.titleA population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland.en
dc.typeArticleen
dc.identifier.eissn1468-6244-
dc.contributor.departmentDepartment of Pathology, University Hospital of Iceland, Reykjavik.en
dc.identifier.journalJournal of medical geneticsen

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