Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
Por:
Fernandez-Rozadilla, C, Alvarez-Barona, M, Quintana, I, Lopez-Novo, A, Amigo, J, Cameselle-Teijeiro, JM, Roman, E, Gonzalez, D, Llor, X, Bujanda, L, Bessa, X, Jover, R, Balaguer, F, Castells, A, Castellvi-Bel, S, Capella, G, Carracedo, A, Valle, L, Ruiz-Ponte, C
Publicada:
27 may 2021
Resumen:
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.
Filiaciones:
Fernandez-Rozadilla, C:
Inst Invest Sanitaria Santiago IDIS, Grp Med Xenom USC, Santiago De Compostela, Spain
Alvarez-Barona, M:
Inst Invest Sanitaria Santiago IDIS, Grp Med Xenom USC, Santiago De Compostela, Spain
Quintana, I:
IDIBELL, Hereditary Canc Program, Catalan Inst Oncol, Program Mol Mech & Expt Therapy Oncol Oncobell, Barcelona, Spain
Lopez-Novo, A:
Inst Invest Sanitaria Santiago IDIS, Grp Med Xenom USC, Santiago De Compostela, Spain
Amigo, J:
Fdn Publ Galega Med Xenom, Grp Med Xenom USC, Inst Invest Sanitaria Santiago IDIS, SERGAS, Santiago De Compostela, Spain
Cameselle-Teijeiro, JM:
USC, Serv Anat Patol, Hosp Clin Univ, Inst Invest Sanitaria Santiago IDIS, Santiago De Compostela, Spain
Roman, E:
Univ Autonoma Barcelona UAB, Gastroenterol Dept, Hosp St Pau, CIBERehd,Escola Univ Infermeria EUI St Pau, Barcelona, Spain
Gonzalez, D:
Hosp Santa Creu & Sant Pau, Patol Digest, Barcelona, Spain
Llor, X:
Yale Univ, Dept Med, New Haven, CT 06520 USA
Yale Univ, Canc Ctr, New Haven, CT 06520 USA
Bujanda, L:
Univ Basque Country, Hosp Univ Donostia, Inst Biodonostia, CIBEREHD,UPV EHU, San Sebastian, Spain
Bessa, X:
Hosp del Mar, Hosp del Mar Med Res Inst IMIM, Gastroenterol Dept, Barcelona, Spain
Jover, R:
Hosp Gen Univ Alicante, Inst Invest Biomed ISABIAL, Serv Med Digest, Alicante, Spain
Balaguer, F:
Univ Barcelona, Gastroenterol Dept, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin,Ctr Invest Biomed Red Enfermedades Hepa, Barcelona, Spain
Castells, A:
Univ Barcelona, Gastroenterol Dept, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin,Ctr Invest Biomed Red Enfermedades Hepa, Barcelona, Spain
Castellvi-Bel, S:
Univ Barcelona, Gastroenterol Dept, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin,Ctr Invest Biomed Red Enfermedades Hepa, Barcelona, Spain
Capella, G:
Catalan Inst Oncol, Hereditary Canc Program, Program Mol Mech & Expt Therapy Oncol Oncobell, IDIBELL,Ctr Invest Biomed Red Canc CIBERONC, Barcelona, Spain
Carracedo, A:
Fdn Publ Galega Med Xenom, Grp Med Xenom USC, Inst Invest Sanitaria Santiago IDIS, SERGAS,Ctr Invest Biomed Red Enfermedades Raras C, Santiago De Compostela, Spain
Valle, L:
Catalan Inst Oncol, Hereditary Canc Program, Program Mol Mech & Expt Therapy Oncol Oncobell, IDIBELL,Ctr Invest Biomed Red Canc CIBERONC, Barcelona, Spain
Ruiz-Ponte, C:
Fdn Publ Galega Med Xenom, Grp Med Xenom USC, Inst Invest Sanitaria Santiago IDIS, SERGAS,Ctr Invest Biomed Red Enfermedades Raras C, Santiago De Compostela, Spain
gold, Green Published
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