TY - JOUR
T1 - Whole-Exome Sequencing Analysis of Oral Squamous Cell Carcinoma Delineated by Tobacco Usage Habits
AU - Patel, Krishna
AU - Bhat, Firdous Ahmad
AU - Patil, Shankargouda
AU - Routray, Samapika
AU - Mohanty, Neeta
AU - Nair, Bipin
AU - Sidransky, David
AU - Ganesh, Mandakulutur S.
AU - Ray, Jay Gopal
AU - Gowda, Harsha
AU - Chatterjee, Aditi
N1 - Funding Information:
We thank the patients for their generosity and courage. KP was the recipients of a Senior Research Fellow from the Council of Scientific and Industrial Research (CSIR). FB was the recipient of Senior Research Fellow from University Grants Commission (UGC). HG was supported by a career development fellowship from NHMRC (APP1148551).
Funding Information:
We thank the Department of Biotechnology (DBT), Government of India, for research support to the Institute of Bioinformatics (IOB), Bangalore. IOB was supported by DBT Program Support on Neuroproteomics and infrastructure for proteomic data analysis (BT/01/COE/08/05).
Publisher Copyright:
© Copyright © 2021 Patel, Bhat, Patil, Routray, Mohanty, Nair, Sidransky, Ganesh, Ray, Gowda and Chatterjee.
PY - 2021/5/31
Y1 - 2021/5/31
N2 - Oral squamous cell carcinoma (OSCC) is a common cancer of the oral cavity in India. Cigarette smoking and chewing tobacco are known risk factors associated with OSCC. However, genomic alterations in OSCC with varied tobacco consumption history are not well-characterized. In this study, we carried out whole-exome sequencing to characterize the mutational landscape of OSCC tumors from subjects with different tobacco consumption habits. We identified several frequently mutated genes, including TP53, NOTCH1, CASP8, RYR2, LRP2, CDKN2A, and ATM. TP53 and HRAS exhibited mutually exclusive mutation patterns. We identified recurrent amplifications in the 1q31, 7q35, 14q11, 22q11, and 22q13 regions and observed amplification of EGFR in 25% of samples with tobacco consumption history. We observed genomic alterations in several genes associated with PTK6 signaling. We observed alterations in clinically actionable targets including ERBB4, HRAS, EGFR, NOTCH1, NOTCH4, and NOTCH3. We observed enrichment of signature 29 in 40% of OSCC samples from tobacco chewers. Signature 15 associated with defective DNA mismatch repair was enriched in 80% of OSCC samples. NOTCH1 was mutated in 36% of samples and harbored truncating as well as missense variants. We observed copy number alterations in 67% of OSCC samples. Several genes associated with non-receptor tyrosine kinase signaling were affected in OSCC. These molecules can serve as potential candidates for therapeutic targeting in OSCC.
AB - Oral squamous cell carcinoma (OSCC) is a common cancer of the oral cavity in India. Cigarette smoking and chewing tobacco are known risk factors associated with OSCC. However, genomic alterations in OSCC with varied tobacco consumption history are not well-characterized. In this study, we carried out whole-exome sequencing to characterize the mutational landscape of OSCC tumors from subjects with different tobacco consumption habits. We identified several frequently mutated genes, including TP53, NOTCH1, CASP8, RYR2, LRP2, CDKN2A, and ATM. TP53 and HRAS exhibited mutually exclusive mutation patterns. We identified recurrent amplifications in the 1q31, 7q35, 14q11, 22q11, and 22q13 regions and observed amplification of EGFR in 25% of samples with tobacco consumption history. We observed genomic alterations in several genes associated with PTK6 signaling. We observed alterations in clinically actionable targets including ERBB4, HRAS, EGFR, NOTCH1, NOTCH4, and NOTCH3. We observed enrichment of signature 29 in 40% of OSCC samples from tobacco chewers. Signature 15 associated with defective DNA mismatch repair was enriched in 80% of OSCC samples. NOTCH1 was mutated in 36% of samples and harbored truncating as well as missense variants. We observed copy number alterations in 67% of OSCC samples. Several genes associated with non-receptor tyrosine kinase signaling were affected in OSCC. These molecules can serve as potential candidates for therapeutic targeting in OSCC.
KW - HNSCC
KW - M-class cancer
KW - genome aberration
KW - mutational signature
KW - oral cancer
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UR - http://www.scopus.com/inward/citedby.url?scp=85107818478&partnerID=8YFLogxK
U2 - 10.3389/fonc.2021.660696
DO - 10.3389/fonc.2021.660696
M3 - Article
C2 - 34136393
AN - SCOPUS:85107818478
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 660696
ER -