Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables

2.50
Hdl Handle:
http://hdl.handle.net/2336/13598
Title:
Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables
Authors:
Johannsdottir, Hrefna K; Johannesdottir, Gudrun; Agnarsson, Bjarni A; Eerola, Hannaleena; Arason, Adalgeir; Johannsson, Oskar T H; Heikkilä, Päivi; Egilsson, Valgardur; Olsson, Hakan; Borg, Ake; Nevanlinna, Heli; Barkardottir, Rosa B
Citation:
Anticancer Res. 2004, 24(5A):2681-7
Issue Date:
1-Oct-2004
Abstract:
BACKGROUND: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes. MATERIALS AND METHODS: In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n=41) as well as in tumors from BRCA2 (n=66) mutation carriers and in tumors from unselected cases of breast cancer (n =68). RESULTS: The frequency of LOH in these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2-associated tumors and 8-33% in unselected tumors. LOH was significantly more frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological variables that were found significantly associated (p< or =0.05) with LOH at specific markers were: high percentage of cells in S-phase, negative estrogen receptor status, young age at diagnosis and large tumors. Deletion mapping indicates the existence of seven non-overlapping regions at chromosome 4, which were identified in all three groups of tumors. Three of these seven regions, 4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast cancer previously. CONCLUSION: The results manifest the frequent alterations of chromosome 4 in BRCA1-associated breast tumors and indicate the location of several genes of potential importance in breast cancer development.
Description:
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Full metadata record

DC FieldValue Language
dc.contributor.authorJohannsdottir, Hrefna K-
dc.contributor.authorJohannesdottir, Gudrun-
dc.contributor.authorAgnarsson, Bjarni A-
dc.contributor.authorEerola, Hannaleena-
dc.contributor.authorArason, Adalgeir-
dc.contributor.authorJohannsson, Oskar T H-
dc.contributor.authorHeikkilä, Päivi-
dc.contributor.authorEgilsson, Valgardur-
dc.contributor.authorOlsson, Hakan-
dc.contributor.authorBorg, Ake-
dc.contributor.authorNevanlinna, Heli-
dc.contributor.authorBarkardottir, Rosa B-
dc.date.accessioned2007-09-12T14:39:13Z-
dc.date.available2007-09-12T14:39:13Z-
dc.date.issued2004-10-01-
dc.date.submitted2007-09-12-
dc.identifier.citationAnticancer Res. 2004, 24(5A):2681-7en
dc.identifier.issn0250-7005-
dc.identifier.pmid15521105-
dc.identifier.urihttp://hdl.handle.net/2336/13598-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes. MATERIALS AND METHODS: In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n=41) as well as in tumors from BRCA2 (n=66) mutation carriers and in tumors from unselected cases of breast cancer (n =68). RESULTS: The frequency of LOH in these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2-associated tumors and 8-33% in unselected tumors. LOH was significantly more frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological variables that were found significantly associated (p< or =0.05) with LOH at specific markers were: high percentage of cells in S-phase, negative estrogen receptor status, young age at diagnosis and large tumors. Deletion mapping indicates the existence of seven non-overlapping regions at chromosome 4, which were identified in all three groups of tumors. Three of these seven regions, 4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast cancer previously. CONCLUSION: The results manifest the frequent alterations of chromosome 4 in BRCA1-associated breast tumors and indicate the location of several genes of potential importance in breast cancer development.en
dc.language.isoenen
dc.publisherJ.G. Delinassios, Anticancer Researchen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshChromosomes, Human, Pair 4en
dc.subject.meshDNA, Neoplasmen
dc.subject.meshGene Deletionen
dc.subject.meshGenes, BRCA1en
dc.subject.meshGenes, BRCA2en
dc.subject.meshGerm-Line Mutationen
dc.subject.meshLoss of Heterozygosityen
dc.subject.meshNucleic Acid Hybridizationen
dc.titleDeletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variablesen
dc.typeArticleen
dc.format.digYES-

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