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Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia

INTRODUCTION: Colorectal cancer arises in a multistep process of carcinogenesis from normal mucosa. The earliest precursor might be a morphologically inconspicuous precancerous field, harboring cancer-associated mutations. METHODS: We systematically analyzed genetic alterations in 77 tissue samples...

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Autores principales: Zhan, Tianzuo, Belle, Sebastian, Valentini, Erica, Herrmann, Simon, Miersch, Thilo, Li, Moying, Gaiser, Timo, Boutros, Michael, Ebert, Matthias P., Betge, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386331/
https://www.ncbi.nlm.nih.gov/pubmed/32764203
http://dx.doi.org/10.14309/ctg.0000000000000212
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author Zhan, Tianzuo
Belle, Sebastian
Valentini, Erica
Herrmann, Simon
Miersch, Thilo
Li, Moying
Gaiser, Timo
Boutros, Michael
Ebert, Matthias P.
Betge, Johannes
author_facet Zhan, Tianzuo
Belle, Sebastian
Valentini, Erica
Herrmann, Simon
Miersch, Thilo
Li, Moying
Gaiser, Timo
Boutros, Michael
Ebert, Matthias P.
Betge, Johannes
author_sort Zhan, Tianzuo
collection PubMed
description INTRODUCTION: Colorectal cancer arises in a multistep process of carcinogenesis from normal mucosa. The earliest precursor might be a morphologically inconspicuous precancerous field, harboring cancer-associated mutations. METHODS: We systematically analyzed genetic alterations in 77 tissue samples from 30 patients with sporadic colorectal neoplasms (18 large adenomas and 12 adenocarcinomas) and matched adjacent normal mucosa (N = 30), as well as normal rectal tissue (N = 17). We profiled mutations associated with colorectal cancer by targeted sequencing of 46 genetic loci using 157 custom amplicons and a median depth of 42,655 reads per loci. RESULTS: Multiple mutations were found in colorectal neoplasms, most frequently in APC, KRAS, and TP53. In a subgroup of 11 of 30 patients, alterations were also detected in non-neoplastic mucosa. These mutations were divergent from those in matched neoplasms. The total alteration count and the allele frequency of mutations were higher in neoplasms compared with those in adjacent tissues. We found that younger patients (≤70 years) are less likely affected by mutations in non-neoplastic mucosa than older patients (>70 years, P = 0.013), although no association was found for other variables, including type, location and differentiation of neoplasia, and previous history of polyps. DISCUSSION: Our data show that cancer-associated mutations can be found in non-neoplastic tissues in a subgroup of patients with colorectal neoplasms. Further studies are needed to specify the risk of occurrence and recurrence of neoplasia in this patient population.
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spelling pubmed-73863312020-08-05 Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia Zhan, Tianzuo Belle, Sebastian Valentini, Erica Herrmann, Simon Miersch, Thilo Li, Moying Gaiser, Timo Boutros, Michael Ebert, Matthias P. Betge, Johannes Clin Transl Gastroenterol Article INTRODUCTION: Colorectal cancer arises in a multistep process of carcinogenesis from normal mucosa. The earliest precursor might be a morphologically inconspicuous precancerous field, harboring cancer-associated mutations. METHODS: We systematically analyzed genetic alterations in 77 tissue samples from 30 patients with sporadic colorectal neoplasms (18 large adenomas and 12 adenocarcinomas) and matched adjacent normal mucosa (N = 30), as well as normal rectal tissue (N = 17). We profiled mutations associated with colorectal cancer by targeted sequencing of 46 genetic loci using 157 custom amplicons and a median depth of 42,655 reads per loci. RESULTS: Multiple mutations were found in colorectal neoplasms, most frequently in APC, KRAS, and TP53. In a subgroup of 11 of 30 patients, alterations were also detected in non-neoplastic mucosa. These mutations were divergent from those in matched neoplasms. The total alteration count and the allele frequency of mutations were higher in neoplasms compared with those in adjacent tissues. We found that younger patients (≤70 years) are less likely affected by mutations in non-neoplastic mucosa than older patients (>70 years, P = 0.013), although no association was found for other variables, including type, location and differentiation of neoplasia, and previous history of polyps. DISCUSSION: Our data show that cancer-associated mutations can be found in non-neoplastic tissues in a subgroup of patients with colorectal neoplasms. Further studies are needed to specify the risk of occurrence and recurrence of neoplasia in this patient population. Wolters Kluwer 2020-07-21 /pmc/articles/PMC7386331/ /pubmed/32764203 http://dx.doi.org/10.14309/ctg.0000000000000212 Text en © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Zhan, Tianzuo
Belle, Sebastian
Valentini, Erica
Herrmann, Simon
Miersch, Thilo
Li, Moying
Gaiser, Timo
Boutros, Michael
Ebert, Matthias P.
Betge, Johannes
Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia
title Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia
title_full Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia
title_fullStr Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia
title_full_unstemmed Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia
title_short Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia
title_sort cancer-associated mutations in normal colorectal mucosa adjacent to sporadic neoplasia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386331/
https://www.ncbi.nlm.nih.gov/pubmed/32764203
http://dx.doi.org/10.14309/ctg.0000000000000212
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