Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer

Abstract 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...

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Autores principales:	C. Fernández-Rozadilla, M. Álvarez-Barona, I. Quintana, A. López-Novo, J. Amigo, J. M. Cameselle-Teijeiro, E. Roman, D. Gonzalez, X. Llor, L. Bujanda, X. Bessa, R. Jover, F. Balaguer, A. Castells, S. Castellví-Bel, G. Capellá, A. Carracedo, L. Valle, Clara Ruiz-Ponte
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a336233f77f4df2a8dd367041fb7916
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spelling	oai:doaj.org-article:1a336233f77f4df2a8dd367041fb79162021-12-02T15:49:42ZExome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer10.1038/s41598-021-90590-z2045-2322https://doaj.org/article/1a336233f77f4df2a8dd367041fb79162021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90590-zhttps://doaj.org/toc/2045-2322Abstract 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.C. Fernández-RozadillaM. Álvarez-BaronaI. QuintanaA. López-NovoJ. AmigoJ. M. Cameselle-TeijeiroE. RomanD. GonzalezX. LlorL. BujandaX. BessaR. JoverF. BalaguerA. CastellsS. Castellví-BelG. CapelláA. CarracedoL. ValleClara Ruiz-PonteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q C. Fernández-Rozadilla M. Álvarez-Barona I. Quintana A. López-Novo J. Amigo J. M. Cameselle-Teijeiro E. Roman D. Gonzalez X. Llor L. Bujanda X. Bessa R. Jover F. Balaguer A. Castells S. Castellví-Bel G. Capellá A. Carracedo L. Valle Clara Ruiz-Ponte Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
description	Abstract 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.
format	article
author	C. Fernández-Rozadilla M. Álvarez-Barona I. Quintana A. López-Novo J. Amigo J. M. Cameselle-Teijeiro E. Roman D. Gonzalez X. Llor L. Bujanda X. Bessa R. Jover F. Balaguer A. Castells S. Castellví-Bel G. Capellá A. Carracedo L. Valle Clara Ruiz-Ponte
author_facet	C. Fernández-Rozadilla M. Álvarez-Barona I. Quintana A. López-Novo J. Amigo J. M. Cameselle-Teijeiro E. Roman D. Gonzalez X. Llor L. Bujanda X. Bessa R. Jover F. Balaguer A. Castells S. Castellví-Bel G. Capellá A. Carracedo L. Valle Clara Ruiz-Ponte
author_sort	C. Fernández-Rozadilla
title	Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
title_short	Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
title_full	Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
title_fullStr	Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
title_full_unstemmed	Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
title_sort	exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1a336233f77f4df2a8dd367041fb7916
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Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer

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