Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer
Autor: | Díaz Gay, Marcos, Franch Expósito, Sebastià, Arnau Collell, Coral, Park, Solip, Supek, Fran, Muñoz, Jenifer, Bonjoch, Laia, Gratacós Mulleras, Anna, Sánchez Rojas, Paula A., Esteban-Jurado, Clara, Ocaña, Teresa, Cuatrecasas, Miriam, Vila Casadesús, Maria, Lozano, Juan José, Parra, Genis, Laurie, Steve, Beltran, Sergi, EPICOLON Consortium, Castells, Antoni, Bujanda Fernández de Pierola, Luis, Cubiella, Joaquín, Balaguer, Francesc, Castellví-Bel, Sergi |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
predisposition to disease Cancer Research Candidate gene ADN colorectal cancer mutational signatures Biology computational genomics lcsh:RC254-282 Germline Article Loss of heterozygosity 03 medical and health sciences germline-tumor analysis 0302 clinical medicine Càncer colorectal Copy-number variation whole-exome sequencing Indel Gene Exome sequencing Genetics Nucleotides DNA lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Colorectal cancer digestive system diseases Nucleòtids 030104 developmental biology Oncology 030220 oncology & carcinogenesis ERCC2 germline–tumor analysis |
Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Cancers Cancers, Vol 11, Iss 3, p 362 (2019) Volume 11 Issue 3 Addi. Archivo Digital para la Docencia y la Investigación instname |
Popis: | Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson&rsquo s two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates. |
Databáze: | OpenAIRE |
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