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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Rare germline alterations in cancer-related genes associated with the risk of multiple primary tumor development

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Villacis, Rolando A. R. ; Basso, Tatiane R. ; Canto, Luisa M. ; Pinheiro, Maisa ; Santiago, Karina M. ; Giacomazzi, Juliana ; de Paula, Claudia A. A. ; Carraro, Dirce M. ; Ashton-Prolla, Patricia ; Achatz, Maria I. ; Rogatto, Silvia R.
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 95, n. 5, p. 523-533, MAY 2017.
Citações Web of Science: 2
Resumo

Multiple primary tumors (MPT) have been described in carriers of inherited cancer predisposition genes. However, the genetic etiology of a large proportion of MPT cases remains unclear. We reviewed 267 patients with hereditary cancer predisposition syndromes (HCPS) that underwent genetic counseling and selected 22 patients with MPT to perform genomic analysis (CytoScan HD Array, Affymetrix) aiming to identify new alterations related to a high risk of developing MPT. Twenty patients had a positive family history of cancer and 11 met phenotypic criteria for HCPS. Genetic testing for each of the genes associated with these syndromes revealed negative results for pathogenic mutations. Seventeen rare germline copy number variations (CNVs) covering 40 genes were identified in 11 patients, including an EPCAM/MSH2 deletion in one Lynch syndrome patient. An enrichment analysis revealed a significant number of genes (where the CNVs are mapped) associated with carcinogenesis and/or related to functions implicated with tumor development, such as proliferation and cell survival. An interaction network analysis highlighted the importance of TP53 pathway in cancer emergence. A high number of germline copy-neutral loss of heterozygosity (cnLOH) was identified in nine cases, particularly in two patients. Eighteen genes were covered by both rare CNVs and cnLOH, including 14 related to tumorigenesis and seven genes (ABCC1, KDM4C, KIAA0430, MYH11, NDE1, PIWIL2, and ULK2) specifically associated with cellular growth and proliferation. Overall, we identified 14 cases with rare CNVs and/or cnLOH that may contribute to the risk of MPT development. (AU)

Processo FAPESP: 08/57887-9 - Instituto Nacional de Oncogenômica
Beneficiário:Luiz Paulo Kowalski
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/23277-8 - Aspectos moleculares envolvidos no risco, desenvolvimento e progressão do carcinoma ductal de mama: busca de novos genes de susceptibilidade e investigação da progressão do carcinoma in situ e do papel da mutação em BRCA1 no tumor triplo negativo
Beneficiário:Dirce Maria Carraro
Linha de fomento: Auxílio à Pesquisa - Temático