Ultrasensitive Detection of Tumor-Specific Mutations in Saliva of Patients With Oral Cavity Squamous Cell Carcinoma

Solomon, Monica C (2021) Ultrasensitive Detection of Tumor-Specific Mutations in Saliva of Patients With Oral Cavity Squamous Cell Carcinoma. Cancer, 127. pp. 1576-1589. ISSN 0008-543X

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BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck malignancy. Although the survival rate of patients with advanced-stage disease remains approximately 20% to 60%, when detected at an early stage, the survival rate approaches 80%, posing a pressing need for a well validated profiling method to assess patients who have a high risk of developing OCSCC.Tumor DNA detection in saliva may provide a robust biomarker platform that overcomes the limitations of current diagnostic tests.However, there is no routine saliva-based screening method for patients with OCSCC. METHODS: The authors designed a custom nextgeneration sequencing panel with unique molecular identifiers that covers coding regions of 7 frequently mutated genes in OCSCC and applied it on DNA extracted from 121 treatment-naive OCSCC tumors and matched preoperative saliva specimens. RESULTS: By using stringent variant-calling criteria, mutations were detected in 106 tumors, consistent with a predicted detection rate ≥88%. Moreover,mutations identified in primary malignancies were also detected in 93% of saliva samples. To ensure that variants are not errors resulting in false-positive calls, a multistep analytical validation of this approach was performed: 1) re-sequencing of 46 saliva samples confirmed 88% of somatic variants; 2) no functionally relevant mutations were detected in saliva samples from 11 healthy individuals without a history of tobacco or alcohol; and 3) using a panel of 7 synthetic loci across 8 sequencing runs, it was confirmed that the platform developed is reproducible and provides sensitivity on par with droplet digital polymerase chain reaction. CONCLUSIONS: The current data highlight the feasibility of somatic mutation identification in driver genes in saliva collected at the time of OCSCC diagnosis

Item Type: Article
Uncontrolled Keywords: Early detection; Liquid biopsy; Mutation; Next-generation sequencing (NGS); Oral cavity squamous cell carcinoma (OCSCC); Oral rinse, saliva
Subjects: Dentistry > MCODS Manipal > Oral Pathology and Microbiology
Depositing User: KMC Library
Date Deposited: 08 Sep 2021 10:35
Last Modified: 08 Sep 2021 10:35
URI: http://eprints.manipal.edu/id/eprint/157290

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