Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma

Abstract Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S., 75% of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) are of African descent. African American ESCC (AA ESCC) is...

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Autores principales:	Hayriye Verda Erkizan, Shrey Sukhadia, Thanemozhi G. Natarajan, Gustavo Marino, Vicente Notario, Jack H. Lichy, Robert G. Wadleigh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca8d62a5f3954af2b113cef1574f176b
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spelling	oai:doaj.org-article:ca8d62a5f3954af2b113cef1574f176b2021-12-02T16:50:24ZExome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma10.1038/s41598-021-94064-02045-2322https://doaj.org/article/ca8d62a5f3954af2b113cef1574f176b2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94064-0https://doaj.org/toc/2045-2322Abstract Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S., 75% of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) are of African descent. African American ESCC (AA ESCC) is particularly aggressive, and its biological underpinnings remain poorly understood. We sought to identify the genomic abnormalities by conducting whole exome sequencing of 10 pairs of matched AA esophageal squamous cell tumor and control tissues. Genomic analysis revealed diverse somatic mutations, copy number alterations (SCNAs), and potential cancer driver genes. Exome variants created two subgroups carrying either a high or low tumor mutation burden. Somatic mutational analysis based on the Catalog of Somatic Mutations in Cancer (COSMIC) detected SBS16 as the prominent signature in the high mutation rate group suggesting increased DNA damage. SBS26 was also detected, suggesting possible defects in mismatch repair and microsatellite instability. We found SCNAs in multiple chromosome segments, encoding MYC on 8q24.21, PIK3CA and SOX2 on 3q26, CCND1, SHANK2, CTTN on 11q13.3, and KRAS on 12p12. Amplifications of EGFRvIII and EGFRvIVa mutants were observed in two patients, representing a novel finding in ESCC that has potential clinical relevance. This present exome sequencing, which to our knowledge, represents the first comprehensive exome analysis exclusively in AA ESCC, and highlights novel mutated loci that might explain the aggressive nature of AA ESCC and lead to the development of diagnostic and prognostic markers as well as therapeutic targets.Hayriye Verda ErkizanShrey SukhadiaThanemozhi G. NatarajanGustavo MarinoVicente NotarioJack H. LichyRobert G. WadleighNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hayriye Verda Erkizan Shrey Sukhadia Thanemozhi G. Natarajan Gustavo Marino Vicente Notario Jack H. Lichy Robert G. Wadleigh Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma
description	Abstract Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S., 75% of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) are of African descent. African American ESCC (AA ESCC) is particularly aggressive, and its biological underpinnings remain poorly understood. We sought to identify the genomic abnormalities by conducting whole exome sequencing of 10 pairs of matched AA esophageal squamous cell tumor and control tissues. Genomic analysis revealed diverse somatic mutations, copy number alterations (SCNAs), and potential cancer driver genes. Exome variants created two subgroups carrying either a high or low tumor mutation burden. Somatic mutational analysis based on the Catalog of Somatic Mutations in Cancer (COSMIC) detected SBS16 as the prominent signature in the high mutation rate group suggesting increased DNA damage. SBS26 was also detected, suggesting possible defects in mismatch repair and microsatellite instability. We found SCNAs in multiple chromosome segments, encoding MYC on 8q24.21, PIK3CA and SOX2 on 3q26, CCND1, SHANK2, CTTN on 11q13.3, and KRAS on 12p12. Amplifications of EGFRvIII and EGFRvIVa mutants were observed in two patients, representing a novel finding in ESCC that has potential clinical relevance. This present exome sequencing, which to our knowledge, represents the first comprehensive exome analysis exclusively in AA ESCC, and highlights novel mutated loci that might explain the aggressive nature of AA ESCC and lead to the development of diagnostic and prognostic markers as well as therapeutic targets.
format	article
author	Hayriye Verda Erkizan Shrey Sukhadia Thanemozhi G. Natarajan Gustavo Marino Vicente Notario Jack H. Lichy Robert G. Wadleigh
author_facet	Hayriye Verda Erkizan Shrey Sukhadia Thanemozhi G. Natarajan Gustavo Marino Vicente Notario Jack H. Lichy Robert G. Wadleigh
author_sort	Hayriye Verda Erkizan
title	Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma
title_short	Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma
title_full	Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma
title_fullStr	Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma
title_full_unstemmed	Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma
title_sort	exome sequencing identifies novel somatic variants in african american esophageal squamous cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca8d62a5f3954af2b113cef1574f176b
work_keys_str_mv	AT hayriyeverdaerkizan exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma AT shreysukhadia exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma AT thanemozhignatarajan exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma AT gustavomarino exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma AT vicentenotario exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma AT jackhlichy exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma AT robertgwadleigh exomesequencingidentifiesnovelsomaticvariantsinafricanamericanesophagealsquamouscellcarcinoma
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Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma

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