Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
| Autor: | Fernández-Rozadilla, C., Álvarez-Barona, M., Quintana, I., López-Novo, A., Amigo, J., Cameselle-Teijeiro, J. M., Roman, Eva, Gonzalez, D., Llor, X., Bujanda, Luis, Bessa Caserras, Xavier, Jover, R., Balaguer, F., Castells, Antoni, Castellví-Bel, S., Capellá, G. (Gabriel), Carracedo, A., Valle, L., Ruiz-Ponte, Clara, Universitat Autònoma de Barcelona |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Metiltransferases Colorectal cancer Science Protein Tyrosine Phosphatase Non-Receptor Type 13 colorectal cancer Disease Biology Article Genetic Heterogeneity Càncer colorectal Exome Sequencing medicine Genetics Humans Exome Genetic Predisposition to Disease Allele Poly-ADP-Ribose Binding Proteins Gene Exome sequencing novel genetic variants Tumors Cancer Multidisciplinary Genetic heterogeneity DNA Helicases potential risk alleles Methyltransferases Middle Aged medicine.disease Còlon--Càncer DNA-Binding Proteins Gene Expression Regulation Neoplastic penetrance changes DNA Repair Enzymes Medicine Female ERCC6 Colorectal Neoplasms Genètica |
| Zdroj: | Scientific Reports r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname Addi. Archivo Digital para la Docencia y la Investigación Dipòsit Digital de la UB Universidad de Barcelona Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Addi: Archivo Digital para la Docencia y la Investigación Universidad del País Vasco SCIENTIFIC REPORTS r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| ISSN: | 2045-2322 |
| Popis: | Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight. This research was supported by Grants from Instituto de Salud Carlos III /FEDER: PI11/00681 (CRP), PI16/01057 (AC), PI17/00509 (CRP), PI17/00878 (SCB), PI19/00179 (CFR), PI19/01316 (JMC-T), PI20/01113 (SCB), PI20/00226 (CRP); CIBERONC-CB16/12/00234 (LV); and Fundación Olga Torres (LV and CFR); CERCA Program and Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya, GRPRE 2017SGR21, GRC 2017SGR653). AL-N is supported by a Predoctoral Fellowship (GAIN, Xunta de Galicia, 2018 call) and IQ is supported by the FPI program of the Spanish Ministry of Science and Innovation—FEDER (SAF2016-80888-R). This article is based upon work from COST Action TransColonCan CA17118, supported by European Cooperation in Science and Technology (COST—www.cost.eu; www.transcoloncan.eu). |
| Databáze: | OpenAIRE |
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