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Enhancing the landscape of colorectal cancer using targeted deep sequencing
Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association wit...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046812/ https://www.ncbi.nlm.nih.gov/pubmed/33854094 http://dx.doi.org/10.1038/s41598-021-87486-3 |
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author | Lee, Chul Seung Song, In Hye Lee, Ahwon Kang, Jun Lee, Yoon Suk Lee, In Kyu Song, Young Soo Lee, Sung Hak |
author_facet | Lee, Chul Seung Song, In Hye Lee, Ahwon Kang, Jun Lee, Yoon Suk Lee, In Kyu Song, Young Soo Lee, Sung Hak |
author_sort | Lee, Chul Seung |
collection | PubMed |
description | Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy. |
format | Online Article Text |
id | pubmed-8046812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80468122021-04-15 Enhancing the landscape of colorectal cancer using targeted deep sequencing Lee, Chul Seung Song, In Hye Lee, Ahwon Kang, Jun Lee, Yoon Suk Lee, In Kyu Song, Young Soo Lee, Sung Hak Sci Rep Article Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy. Nature Publishing Group UK 2021-04-14 /pmc/articles/PMC8046812/ /pubmed/33854094 http://dx.doi.org/10.1038/s41598-021-87486-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lee, Chul Seung Song, In Hye Lee, Ahwon Kang, Jun Lee, Yoon Suk Lee, In Kyu Song, Young Soo Lee, Sung Hak Enhancing the landscape of colorectal cancer using targeted deep sequencing |
title | Enhancing the landscape of colorectal cancer using targeted deep sequencing |
title_full | Enhancing the landscape of colorectal cancer using targeted deep sequencing |
title_fullStr | Enhancing the landscape of colorectal cancer using targeted deep sequencing |
title_full_unstemmed | Enhancing the landscape of colorectal cancer using targeted deep sequencing |
title_short | Enhancing the landscape of colorectal cancer using targeted deep sequencing |
title_sort | enhancing the landscape of colorectal cancer using targeted deep sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046812/ https://www.ncbi.nlm.nih.gov/pubmed/33854094 http://dx.doi.org/10.1038/s41598-021-87486-3 |
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