ROBO1 deletion as a novel germline alteration in breast and colorectal cancer patients

Página do item simplificado
dc.contributor.authorVillacis, Rolando A R
dc.contributor.authorAbreu, Francine B.
dc.contributor.authorMiranda, Priscila M.
dc.contributor.authorDomingues, Maria A C [UNESP]
dc.contributor.authorCarraro, Dirce M.
dc.contributor.authorSantos, Erika M. M.
dc.contributor.authorAndrade, Victor P.
dc.contributor.authorRossi, Benedito M.
dc.contributor.authorAchatz, Maria I.
dc.contributor.authorRogatto, Silvia Regina [UNESP]
dc.contributor.institutionInternational Research Center (CIPE)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionSírio-Libanês Hospital
dc.contributor.institutionCamargo Cancer Center
dc.date.accessioned2015-12-07T15:38:43Z
dc.date.available2015-12-07T15:38:43Z
dc.date.issued2015-10-01
dc.description.abstractDespite one third of breast (BC) and colorectal cancer (CRC) cases having a hereditary component, only a small proportion can be explained by germline mutations. The aim of this study was to identify potential genomic alterations related to cancer predisposition. Copy number variations (CNVs) were interrogated in 113 unrelated cases fulfilling the criteria for hereditary BC/CRC and presenting non-pathogenic mutations in BRCA1, BRCA2, MLH1, MSH2, TP53, and CHEK2 genes. An identical germline deep intronic deletion of ROBO1 was identified in three index patients using two microarray platforms (Agilent 4x180K and Affymetrix CytoScan HD). The ROBO1 deletion was confirmed by quantitative PCR (qPCR). Six relatives were also evaluated by CytoScan HD Array. Genomic analysis confirmed a co-segregation of the ROBO1 deletion with the occurrence of cancer in two families. Direct sequencing revealed no pathogenic ROBO1 point mutations. Transcriptomic analysis (HTA 2.0, Affymetrix) in two breast carcinomas from a single patient revealed ROBO1 down-expression with no splicing events near the intronic deletion. Deeper in silico analysis showed several enhancer regions and a histone methylation mark in the deleted region. The ROBO1 deletion in a putative transcriptional regulatory region, its down-expression in tumor samples, and the results of the co-segregation analysis revealing the presence of the alteration in affected individuals suggest a pathogenic effect of the ROBO1 in cancer predisposition.en
dc.description.affiliationInternational Research Center (CIPE), A.C. Camargo Cancer Center, Rua Taguá 440, São Paulo, CEP: 01508-010, SP, Brazil.
dc.description.affiliationDepartment of Pathology, Faculty of Medicine, University of São Paulo State (UNESP), Botucatu, SP, Brazil.
dc.description.affiliationOncology Center, Sírio-Libanês Hospital, São Paulo, SP, Brazil.
dc.description.affiliationDepartment of Pathology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
dc.description.affiliationDepartment of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
dc.description.affiliationInternational Research Center (CIPE), A.C. Camargo Cancer Center, Rua Taguá 440, São Paulo, CEP: 01508-010, SP, Brazil.
dc.description.affiliationDepartment of Urology, Faculty of Medicine, University of São Paulo State (UNESP), CEP: 18618-970, Botucatu, SP, Brazil.
dc.description.affiliationUnespDepartment of Pathology, Faculty of Medicine, University of São Paulo State (UNESP), Botucatu, SP, Brazil.
dc.description.affiliationUnespDepartment of Urology, Faculty of Medicine, University of São Paulo State (UNESP), CEP: 18618-970, Botucatu, SP, Brazil.
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2008/57887-9
dc.description.sponsorshipIdCNPq: 573589/08-9
dc.description.sponsorshipIdFAPESP: 2010/15901-5
dc.description.sponsorshipIdFAPESP: 2011/07742-7
dc.format.extent1-9
dc.identifierhttp://dx.doi.org/10.1007/s13277-015-4145-0
dc.identifier.citationTumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine, p. 1-9, 2015.
dc.identifier.doi10.1007/s13277-015-4145-0
dc.identifier.issn1423-0380
dc.identifier.lattes2259986546265579
dc.identifier.pubmed26427657
dc.identifier.urihttp://hdl.handle.net/11449/131615
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofTumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
dc.relation.ispartofsjr1,149
dc.rights.accessRightsAcesso restrito
dc.sourcePubMed
dc.subjectBreast carcinomaen
dc.subjectColorectal canceren
dc.subjectGermline deletionen
dc.subjectHereditary canceren
dc.subjectRobo1en
dc.titleROBO1 deletion as a novel germline alteration in breast and colorectal cancer patientsen
dc.typeArtigo
dcterms.rightsHolderSpringer
unesp.author.lattes2259986546265579
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Medicina, Botucatupt

Arquivos

Coleções

Artigos - Patologia - FMB
Artigos - Urologia - FMB