Chromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation carriers and sporadic breast tumors

2.50
Hdl Handle:
http://hdl.handle.net/2336/6314
Title:
Chromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation carriers and sporadic breast tumors
Authors:
Johannsdottir, Hrefna K; Jonsson, Goran; Johannesdottir, Gudrun; Agnarsson, Bjarni A; Eerola, Hannaleena; Arason, Adalgeir; Heikkila, Paivi; Egilsson, Valgardur; Olsson, Hakan; Johannsson, Oskar Th; Nevanlinna, Heli; Borg, Ake; Barkardottir, Rosa B
Citation:
Int. J. Cancer 2006, 119(5):1052-60
Issue Date:
1-Sep-2006
Abstract:
Comparative genomic hybridization (CGH) analysis has shown that chromosome 5q deletions are the most frequent aberration in breast tumors from BRCA1 mutation carriers. To map the location of putative 5q tumor suppressor gene(s), 26 microsatellite markers covering chromosome 5 were used in loss of heterozygosity (LOH) analysis of breast tumors from BRCA1 (n = 42) and BRCA2 mutation carriers (n = 67), as well as in sporadic cases (n = 65). High-density array CGH was also used to map chromosome 5 imbalance in 10 BRCA1 tumors. A high LOH frequency was found in BRCA1 tumors (range 19-82%), as compared to BRCA2 and sporadic tumors (ranges 11-44% and 7-43%, respectively). In all, 11 distinct chromosome 5 regions with LOH were observed, the most frequent being 5q35.3 (82%), 5q14.2 (71%) and 5q33.1 (69%) in BRCA1 tumors; 5q35.3 (44%), 5q31.3 (43%) and 5q13.3 (43%) in BRCA2 tumors and 5q31.3 (43%) in sporadic tumors. Array CGH analysis confirmed the very high frequency of 5q deletions, including candidate tumor suppressor genes such as XRCC4, RAD50, RASA1, APC and PPP2R2B. In addition, 2 distinct homozygous deletions were identified, spanning regions of 0.7-1.5 Mbp on 5q12.1 and 5q12.3-q13.1, respectively. These regions include only a few genes, most notably BRCC3/DEPDC1B (pleckstrin/G protein interacting and RhoGAP domains) and PIK3R1 (PI3 kinase P85 regulatory subunit). Significant association (p < or = 0.05) was found between LOH at certain 5q regions and factors of poor prognosis, including negative estrogen and progesterone receptor status, high grade, large tumor size and high portion of cells in S-phase. In conclusion, our results confirm a very high prevalence of chromosome 5q alterations in BRCA1 tumors, pinpointing new regions and genes that should be further investigated.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www3.interscience.wiley.com/cgi-bin/fulltext/112570703/HTMLSTART

Full metadata record

DC FieldValue Language
dc.contributor.authorJohannsdottir, Hrefna K-
dc.contributor.authorJonsson, Goran-
dc.contributor.authorJohannesdottir, Gudrun-
dc.contributor.authorAgnarsson, Bjarni A-
dc.contributor.authorEerola, Hannaleena-
dc.contributor.authorArason, Adalgeir-
dc.contributor.authorHeikkila, Paivi-
dc.contributor.authorEgilsson, Valgardur-
dc.contributor.authorOlsson, Hakan-
dc.contributor.authorJohannsson, Oskar Th-
dc.contributor.authorNevanlinna, Heli-
dc.contributor.authorBorg, Ake-
dc.contributor.authorBarkardottir, Rosa B-
dc.date.accessioned2006-11-30T17:16:12Z-
dc.date.available2006-11-30T17:16:12Z-
dc.date.issued2006-09-01-
dc.identifier.citationInt. J. Cancer 2006, 119(5):1052-60en
dc.identifier.issn0020-7136-
dc.identifier.pmid16570289-
dc.identifier.doi10.1002/ijc.21934-
dc.identifier.otherMAO12-
dc.identifier.otherPTT12-
dc.identifier.urihttp://hdl.handle.net/2336/6314-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractComparative genomic hybridization (CGH) analysis has shown that chromosome 5q deletions are the most frequent aberration in breast tumors from BRCA1 mutation carriers. To map the location of putative 5q tumor suppressor gene(s), 26 microsatellite markers covering chromosome 5 were used in loss of heterozygosity (LOH) analysis of breast tumors from BRCA1 (n = 42) and BRCA2 mutation carriers (n = 67), as well as in sporadic cases (n = 65). High-density array CGH was also used to map chromosome 5 imbalance in 10 BRCA1 tumors. A high LOH frequency was found in BRCA1 tumors (range 19-82%), as compared to BRCA2 and sporadic tumors (ranges 11-44% and 7-43%, respectively). In all, 11 distinct chromosome 5 regions with LOH were observed, the most frequent being 5q35.3 (82%), 5q14.2 (71%) and 5q33.1 (69%) in BRCA1 tumors; 5q35.3 (44%), 5q31.3 (43%) and 5q13.3 (43%) in BRCA2 tumors and 5q31.3 (43%) in sporadic tumors. Array CGH analysis confirmed the very high frequency of 5q deletions, including candidate tumor suppressor genes such as XRCC4, RAD50, RASA1, APC and PPP2R2B. In addition, 2 distinct homozygous deletions were identified, spanning regions of 0.7-1.5 Mbp on 5q12.1 and 5q12.3-q13.1, respectively. These regions include only a few genes, most notably BRCC3/DEPDC1B (pleckstrin/G protein interacting and RhoGAP domains) and PIK3R1 (PI3 kinase P85 regulatory subunit). Significant association (p < or = 0.05) was found between LOH at certain 5q regions and factors of poor prognosis, including negative estrogen and progesterone receptor status, high grade, large tumor size and high portion of cells in S-phase. In conclusion, our results confirm a very high prevalence of chromosome 5q alterations in BRCA1 tumors, pinpointing new regions and genes that should be further investigated.en
dc.language.isoenen
dc.publisherWiley-Lissen
dc.relation.urlhttp://www3.interscience.wiley.com/cgi-bin/fulltext/112570703/HTMLSTARTen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAllelic Imbalanceen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshChromosome Mappingen
dc.subject.meshChromosomes, Human, Pair 5en
dc.subject.meshFemaleen
dc.subject.meshGene Deletionen
dc.subject.meshGenes, BRCA1en
dc.subject.meshGenes, BRCA2en
dc.subject.meshGerm-Line Mutationen
dc.subject.meshHeterozygoteen
dc.subject.meshHumansen
dc.subject.meshLoss of Heterozygosityen
dc.subject.meshMiddle Ageden
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshResearch Support, Non-U.S. Gov'ten
dc.titleChromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation carriers and sporadic breast tumorsen
dc.typeArticleen
dc.format.digYES-

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