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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Villacis, Rolando A. R. [1] ; Abreu, Francine B. [1] ; Miranda, Priscila M. [1] ; Domingues, Maria A. C. [2] ; Carraro, Dirce M. [1] ; Santos, Erika M. M. [3] ; Andrade, Victor P. [4] ; Rossi, Benedito M. [3] ; Achatz, Maria I. [5] ; Rogatto, Silvia R. [1, 6]
Total Authors: 10
[1] AC Camargo Canc Ctr, Int Res Ctr CIPE, Rua Tagua 440, BR-01508010 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo State UNESP, Fac Med, Dept Pathol, Botucatu, SP - Brazil
[3] Sirio Libanes Hosp, Ctr Oncol, Sao Paulo, SP - Brazil
[4] AC Camargo Canc Ctr, Dept Pathol, Rua Tagua 440, BR-01508010 Sao Paulo, SP - Brazil
[5] AC Camargo Canc Ctr, Dept Oncogenet, Rua Tagua 440, BR-01508010 Sao Paulo, SP - Brazil
[6] Univ Sao Paulo State UNESP, Fac Med, Dept Urol, BR-18618970 Botucatu, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: TUMOR BIOLOGY; v. 37, n. 3, p. 3145-3153, MAR 2016.
Web of Science Citations: 6

Despite 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. (AU)

FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
Grantee:Luiz Paulo Kowalski
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/15901-5 - Evaluation of genomic copy number variation of genes that predispose patients with hereditary breast and colorrectal cancer syndrome screened for mutations in BRCA1, BRCA2, TP53 and CHEK2
Grantee:Francine Blumental de Abreu
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 11/07742-7 - Genomic changes in patients and their relatives with hereditary colorectal cancer syndrome
Grantee:Rolando André Rios Villacis
Support type: Scholarships in Brazil - Doctorate