2.50
Hdl Handle:
http://hdl.handle.net/2336/47357
Title:
Reduced Fhit expression in sporadic and BRCA2-linked breast carcinomas
Authors:
Ingvarsson, S; Agnarsson, B A; Sigbjornsdottir, B I; Kononen, J; Kallioniemi, O P; Barkardottir, R B; Kovatich, A J; Schwarting, R; Hauck, W W; Huebner, K; McCue, P A
Citation:
Cancer Res. 1999, 59(11):2682-9
Issue Date:
1-Jun-1999
Abstract:
Evidence for alteration of the FHIT gene in a significant fraction of breast carcinomas has been reported, in apparent concordance with loss of heterozygosity (LOH) at chromosome region 3p14.2 in breast cancer and benign proliferative breast disease. A significantly higher frequency of LOH at the FHIT locus was reported for BRCA2-/- tumors, possibly due to misrepaired double-strand breaks at this common fragile region. To determine whether such genomic alterations lead to Fhit inactivation, we have assessed the level of Fhit expression by immunohistochemical detection in sporadic tumors and cancers occurring in BRCA2 999del5 carriers. To determine whether Fhit inactivation may have prognostic significance, we have also assessed expression of breast cancer markers and clinical features in sporadic tumors relative to Fhit expression. Of 40 consecutive sporadic breast carcinomas studied for tumor markers, 50% showed reduced Fhit expression. In these sporadic cancers, loss of Fhit expression was not correlated significantly with the presence or absence of other tumor markers. In a study of 58 sporadic and 34 BRCA2 999del5 Icelandic invasive cancers, there was a significant association of LOH at 3p14.2 with reduced expression of Fhit (P = 0.001); also the lower expression of Fhit and higher LOH at 3p14.2 in BRCA2 999del5 tumors relative to sporadic cancers was significant (P = 0.002). Thus, genetic alteration at the fragile site within the FHIT gene leads to loss of Fhit protein in a significant fraction of sporadic breast cancers and a much larger fraction of familial breast cancers with an inherited BRCA2 mutation, consistent with the idea that loss of BRCA2 function affects stability of the FHIT/FRA3B locus.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://cancerres.aacrjournals.org/cgi/content/abstract/59/11/2682

Full metadata record

DC FieldValue Language
dc.contributor.authorIngvarsson, S-
dc.contributor.authorAgnarsson, B A-
dc.contributor.authorSigbjornsdottir, B I-
dc.contributor.authorKononen, J-
dc.contributor.authorKallioniemi, O P-
dc.contributor.authorBarkardottir, R B-
dc.contributor.authorKovatich, A J-
dc.contributor.authorSchwarting, R-
dc.contributor.authorHauck, W W-
dc.contributor.authorHuebner, K-
dc.contributor.authorMcCue, P A-
dc.date.accessioned2009-01-13T13:10:25Z-
dc.date.available2009-01-13T13:10:25Z-
dc.date.issued1999-06-01-
dc.date.submitted2009-01-13-
dc.identifier.citationCancer Res. 1999, 59(11):2682-9en
dc.identifier.issn0008-5472-
dc.identifier.pmid10363992-
dc.identifier.urihttp://hdl.handle.net/2336/47357-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractEvidence for alteration of the FHIT gene in a significant fraction of breast carcinomas has been reported, in apparent concordance with loss of heterozygosity (LOH) at chromosome region 3p14.2 in breast cancer and benign proliferative breast disease. A significantly higher frequency of LOH at the FHIT locus was reported for BRCA2-/- tumors, possibly due to misrepaired double-strand breaks at this common fragile region. To determine whether such genomic alterations lead to Fhit inactivation, we have assessed the level of Fhit expression by immunohistochemical detection in sporadic tumors and cancers occurring in BRCA2 999del5 carriers. To determine whether Fhit inactivation may have prognostic significance, we have also assessed expression of breast cancer markers and clinical features in sporadic tumors relative to Fhit expression. Of 40 consecutive sporadic breast carcinomas studied for tumor markers, 50% showed reduced Fhit expression. In these sporadic cancers, loss of Fhit expression was not correlated significantly with the presence or absence of other tumor markers. In a study of 58 sporadic and 34 BRCA2 999del5 Icelandic invasive cancers, there was a significant association of LOH at 3p14.2 with reduced expression of Fhit (P = 0.001); also the lower expression of Fhit and higher LOH at 3p14.2 in BRCA2 999del5 tumors relative to sporadic cancers was significant (P = 0.002). Thus, genetic alteration at the fragile site within the FHIT gene leads to loss of Fhit protein in a significant fraction of sporadic breast cancers and a much larger fraction of familial breast cancers with an inherited BRCA2 mutation, consistent with the idea that loss of BRCA2 function affects stability of the FHIT/FRA3B locus.en
dc.language.isoenen
dc.publisherAmerican Association for Cancer Researchen
dc.relation.urlhttp://cancerres.aacrjournals.org/cgi/content/abstract/59/11/2682en
dc.subject.meshAcid Anhydride Hydrolasesen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshBRCA2 Proteinen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshChromosomes, Human, Pair 3en
dc.subject.meshFemaleen
dc.subject.meshLoss of Heterozygosityen
dc.subject.meshMicrosatellite Repeatsen
dc.subject.meshMiddle Ageden
dc.subject.meshMutationen
dc.subject.meshNeoplasm Proteinsen
dc.subject.meshProteinsen
dc.subject.meshTranscription Factorsen
dc.titleReduced Fhit expression in sporadic and BRCA2-linked breast carcinomasen
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, University Hospital of Iceland, Reykjavik.en
dc.identifier.journalCancer researchen

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