# Integrated Analysis of Germline and Somatic Mutations in Young, Low-Risk and Older, High-Risk Oral Cavity Cancer

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $250,436

## Abstract

PROJECT SUMMARY/ABSTRACT
 Oral cavity squamous cell carcinoma (OCSCC) is an aggressive and deadly disease. While tobacco
and alcohol abuse are the risk factors of carcinogenesis in traditional high-risk OCSCC patients, there is a
subset of young patients, even in the absence of these risk factors, who develop sporadic OCSCC. The cause
of OCSCC in young patients remains unknown and despite their young age and lack of risk factors have poor
survival. Based on our preliminary data, there appears to be demographic, etiologic, and mutational burden
differences between younger, low-risk (≤40 years, non-smokers and non-drinkers) and traditional, high-risk
(>50 years, >20 pack-years of tobacco use and high alcohol use) patients. We are seeking to utilize genomic
and transcriptomic differences to determine the molecular mechanism of tumorigenesis with a focus on DNA
repair and telomere maintenance pathways in young, low-risk OCSCC.
 The proposed study and training aims are to develop a career development plan that will be critical to
further defining the molecular mechanisms of tumorigenesis through next generation sequencing in young
OCSCC patients. In AIM1, we seek to analyze young, low-risk OCSCC patients (cases) and traditional, high-
risk patients (control) for epidemiologic risk factors and to perform integrated analysis of germline and somatic
variants to further elucidate the genomic impact in OCSCC. We will then use high throughput RNASeq to
analyze the transcriptome in these two groups to further characterize differences or similarities and allow
greater insight into the potential mechanisms of tumorigenesis. In AIM2 we will investigate the impact of
previously identified germline candidate gene mutations in the DNA repair and telomere maintenance
pathways on tumorigenesis and genome instability using genetic editing and in vitro techniques. This study will
allow us to develop and analyze data critical to understanding of OCSCC and to provide me, the P.I., the
opportunity to develop the research tools, fund of knowledge, and skills necessary to perform this type of study
as I seek to become an independently funded clinician-scientist. The P.I. is a head and neck surgical
oncologist and witnesses the daily impact head and neck cancer has on patients, thus recognizes the need to
improve patient care through translational research. The P.I. is an active member of the Head and Neck
oncology program, who is strongly supported by his department, as well as a team of strong bio-informatics
collaborators with significant experience in making substantial changes to the field of cancer genetics. The P.I.
has designed a mentored training and educational program to directly correlate with the research aims to allow
an integrated education for advanced sequencing techniques. Based on our joint experience, we expect our
research to have high potential for translational application to patient care. In summary, this proposal has
significant potential to dramati...

## Key facts

- **NIH application ID:** 9999336
- **Project number:** 5K08CA226350-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Steven Bennett Chinn
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $250,436
- **Award type:** 5
- **Project period:** 2018-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999336

## Citation

> US National Institutes of Health, RePORTER application 9999336, Integrated Analysis of Germline and Somatic Mutations in Young, Low-Risk and Older, High-Risk Oral Cavity Cancer (5K08CA226350-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999336. Licensed CC0.

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