Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines

Understanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li-Han Lin, Chung-Hsien Chou, Hui-Wen Cheng, Kuo-Wei Chang, Chung-Ji Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mutation burden oral cancer somatic mutation survival whole-exome sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5dd5a15432a244049d143d6e181d117e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5dd5a15432a244049d143d6e181d117e
record_format	dspace
spelling	oai:doaj.org-article:5dd5a15432a244049d143d6e181d117e2021-12-01T11:26:12ZPrecise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines2234-943X10.3389/fonc.2021.741626https://doaj.org/article/5dd5a15432a244049d143d6e181d117e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.741626/fullhttps://doaj.org/toc/2234-943XUnderstanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multiple filtering criteria applied to 50 paired OSCC samples. The tumor mutation burden extracted from the data set of somatic variations was significantly associated with age, tumor staging, and survival. Several genes (MUC16, MUC19, KMT2D, TTN, HERC2) with a high frequency of false positive mutations were identified. Moreover, known (TP53, FAT1, EPHA2, NOTCH1, CASP8, and PIK3CA) and novel (HYDIN, ALPK3, ASXL1, USP9X, SKOR2, CPLANE1, STARD9, and NSD2) genes have been found to be significantly and frequently mutated in OSCC. Further analysis of gene alteration status with clinical parameters revealed that canonical pathways, including clathrin-mediated endocytotic signaling, NFκB signaling, PEDF signaling, and calcium signaling were associated with OSCC prognosis. Defining a catalog of targetable genomic alterations showed that 58% of the tumors carried at least one aberrant event that may potentially be targeted by approved therapeutic agents. We found molecular OSCC subgroups which were correlated with etiology and prognosis while defining the landscape of major altered events in the coding regions of OSCC genomes. These findings provide information that will be helpful in the design of clinical trials on targeted therapies and in the stratification of patients with OSCC according to therapeutic efficacy.Li-Han LinChung-Hsien ChouHui-Wen ChengKuo-Wei ChangKuo-Wei ChangChung-Ji LiuChung-Ji LiuFrontiers Media S.A.articlemutation burdenoral cancersomatic mutationsurvivalwhole-exome sequencingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mutation burden oral cancer somatic mutation survival whole-exome sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	mutation burden oral cancer somatic mutation survival whole-exome sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Li-Han Lin Chung-Hsien Chou Hui-Wen Cheng Kuo-Wei Chang Kuo-Wei Chang Chung-Ji Liu Chung-Ji Liu Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
description	Understanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multiple filtering criteria applied to 50 paired OSCC samples. The tumor mutation burden extracted from the data set of somatic variations was significantly associated with age, tumor staging, and survival. Several genes (MUC16, MUC19, KMT2D, TTN, HERC2) with a high frequency of false positive mutations were identified. Moreover, known (TP53, FAT1, EPHA2, NOTCH1, CASP8, and PIK3CA) and novel (HYDIN, ALPK3, ASXL1, USP9X, SKOR2, CPLANE1, STARD9, and NSD2) genes have been found to be significantly and frequently mutated in OSCC. Further analysis of gene alteration status with clinical parameters revealed that canonical pathways, including clathrin-mediated endocytotic signaling, NFκB signaling, PEDF signaling, and calcium signaling were associated with OSCC prognosis. Defining a catalog of targetable genomic alterations showed that 58% of the tumors carried at least one aberrant event that may potentially be targeted by approved therapeutic agents. We found molecular OSCC subgroups which were correlated with etiology and prognosis while defining the landscape of major altered events in the coding regions of OSCC genomes. These findings provide information that will be helpful in the design of clinical trials on targeted therapies and in the stratification of patients with OSCC according to therapeutic efficacy.
format	article
author	Li-Han Lin Chung-Hsien Chou Hui-Wen Cheng Kuo-Wei Chang Kuo-Wei Chang Chung-Ji Liu Chung-Ji Liu
author_facet	Li-Han Lin Chung-Hsien Chou Hui-Wen Cheng Kuo-Wei Chang Kuo-Wei Chang Chung-Ji Liu Chung-Ji Liu
author_sort	Li-Han Lin
title	Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
title_short	Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
title_full	Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
title_fullStr	Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
title_full_unstemmed	Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
title_sort	precise identification of recurrent somatic mutations in oral cancer through whole-exome sequencing using multiple mutation calling pipelines
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5dd5a15432a244049d143d6e181d117e
work_keys_str_mv	AT lihanlin preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines AT chunghsienchou preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines AT huiwencheng preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines AT kuoweichang preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines AT kuoweichang preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines AT chungjiliu preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines AT chungjiliu preciseidentificationofrecurrentsomaticmutationsinoralcancerthroughwholeexomesequencingusingmultiplemutationcallingpipelines
_version_	1718405235320291328

Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines

Ejemplares similares