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Whole-exome sequencing identified mutational profiles of high-grade colon adenomas
Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351654/ https://www.ncbi.nlm.nih.gov/pubmed/28179590 http://dx.doi.org/10.18632/oncotarget.14172 |
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author | Lee, Sung Hak Hyun, Seung Jung Kim, Tae-Min Rhee, Je-Keun Park, Hyeon-Chun Sung, Min Kim Kim, Sung Soo Hyeok, Chang An Lee Hyung, Sug Chung, Yeun-Jun |
author_facet | Lee, Sung Hak Hyun, Seung Jung Kim, Tae-Min Rhee, Je-Keun Park, Hyeon-Chun Sung, Min Kim Kim, Sung Soo Hyeok, Chang An Lee Hyung, Sug Chung, Yeun-Jun |
author_sort | Lee, Sung Hak |
collection | PubMed |
description | Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel adenoma-specific genes but also critical genes for its progression to carcinoma. For this, we performed whole-exome sequencing (WES) of 12 HGCAs and identified 11 non-hypermutated and one hypermutated (POLE-mutated) cases. We identified 22 genes including APC, KRAS, TP53, GNAS, NRAS, SMAD4, ARID2, and PIK3CA with non-silent mutations in the cancer Census Genes. Bi-allelic and mono-allelic APC alterations were found in nine and one HGCAs, respectively, while the other two harbored wild-type APC. Five HGCAs harbored either mono-allelic (four HGCAs) or bi-allelic (one HGCA) SMAD4 mutation or 18q loss that had been known as early carcinoma-specific changes. We identified MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations for the first time in colon adenomas. Our WES data is largely matched with the earlier ‘adenoma-carcinoma model’ (APC, KRAS, NRAS and GNAS mutations), but there are newly identified SMAD4, MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations in this study. Our findings provide resource for understanding colon premalignant lesions and for identifying genomic clues for differential diagnosis and therapy options for colon adenomas and carcinomas. |
format | Online Article Text |
id | pubmed-5351654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53516542017-04-13 Whole-exome sequencing identified mutational profiles of high-grade colon adenomas Lee, Sung Hak Hyun, Seung Jung Kim, Tae-Min Rhee, Je-Keun Park, Hyeon-Chun Sung, Min Kim Kim, Sung Soo Hyeok, Chang An Lee Hyung, Sug Chung, Yeun-Jun Oncotarget Research Paper Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel adenoma-specific genes but also critical genes for its progression to carcinoma. For this, we performed whole-exome sequencing (WES) of 12 HGCAs and identified 11 non-hypermutated and one hypermutated (POLE-mutated) cases. We identified 22 genes including APC, KRAS, TP53, GNAS, NRAS, SMAD4, ARID2, and PIK3CA with non-silent mutations in the cancer Census Genes. Bi-allelic and mono-allelic APC alterations were found in nine and one HGCAs, respectively, while the other two harbored wild-type APC. Five HGCAs harbored either mono-allelic (four HGCAs) or bi-allelic (one HGCA) SMAD4 mutation or 18q loss that had been known as early carcinoma-specific changes. We identified MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations for the first time in colon adenomas. Our WES data is largely matched with the earlier ‘adenoma-carcinoma model’ (APC, KRAS, NRAS and GNAS mutations), but there are newly identified SMAD4, MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations in this study. Our findings provide resource for understanding colon premalignant lesions and for identifying genomic clues for differential diagnosis and therapy options for colon adenomas and carcinomas. Impact Journals LLC 2016-12-25 /pmc/articles/PMC5351654/ /pubmed/28179590 http://dx.doi.org/10.18632/oncotarget.14172 Text en Copyright: © 2017 Lee et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Lee, Sung Hak Hyun, Seung Jung Kim, Tae-Min Rhee, Je-Keun Park, Hyeon-Chun Sung, Min Kim Kim, Sung Soo Hyeok, Chang An Lee Hyung, Sug Chung, Yeun-Jun Whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
title | Whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
title_full | Whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
title_fullStr | Whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
title_full_unstemmed | Whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
title_short | Whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
title_sort | whole-exome sequencing identified mutational profiles of high-grade colon adenomas |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351654/ https://www.ncbi.nlm.nih.gov/pubmed/28179590 http://dx.doi.org/10.18632/oncotarget.14172 |
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