Oral dysplasias to carcinomas: multi-omics study of progression

Active Cooperative Agreement Awarded Last action

Award ID
U01DE033348
Recipient
Awarding agency
Obligated
$4,734,316

Award facts

Assistance listing
93.121 Oral Diseases and Disorders Research
Completion date 65% complete
Place of performance
Washington, DC 20057, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Oral squamous cell carcinomas (OSCCS) account for 35-38% of head and neck SCC, the 6TH most common cancer worldwide, and have a disappointing 5-year survival rate of ~50%. Oral epithelial dysplasia (OED) are precursors to oscc, but many go undiagnosed. Studies of OED allow characterization of the aberrant molecular changes that lead to cancer. Yet due to inconsistencies in standard care and a lack of sufficient longitudinal data, few studies have examined the molecular characteristics that drive the transformation of OED to oscc across time in the same patients to identify features unique to recurrence with progression. There are very few longitudinal studies of OED progression, and those that exist have little epidemiologic characterization and lack data integration from multi-omics. Additionally, existing reports concentrate on a few common candidate genes and/or are limited to a small sample size. We will use our uniquely detailed longitudinal cohort of OED to integrate clinical, histopathologic, epidemiologic and multiple molecular characteristics of OED lesions to identify those hallmarks of OED lesions that lead to oscc. This will benefit patients by leading to improved risk prediction, more effective preventive measures, and insight into oscc biomarkers that indicate carcinogenesis. Use of a large, highly-characterized longitudinal cohort for this type of multi-omics study, while using a second, independent population to validate generalizability, is highly innovative. Viewed in light of the molecular profiles of OSCCS identified from our current set of tumors and from tcga hnsc data, this study will enable US to focus on the most relevant, recurrent changes, and understand how OSCCS that proceed OED fit into the heterogeneity of overall OSCCS. Identification of biomarkers predictive of progression will enable clinicians to provide more targeted preventive measures, and vary the extensiveness of surgery and frequency of monitoring to increase quality of life. In aim 1, we will use existing samples identify genomic, transcriptomic, and epigenetic profile signatures distinguishing progressors from non-progressors at diagnosis for each OED stage. Our approach allows US to identify a set of candidate biomarkers that distinguish high from low risk lesions, accounting for important biologic variables. The goal of aim 2 is to chart the timing of key genomic, transcriptomic, and epigenetic changes associated with progression to oscc, using extensive longitudinal cases, and comparing observed changes to genes and pathways known to be aberrant in oscc. In aim 3, we will validate the characterization of our unique longitudinal clinical cohort in OED with and without a subsequent diagnosis of oscc from the university of michigan to identify clinicopathologic and epidemiologic predictors of recurrence with progression.

Transactions

Action Obligated Date
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Amendment $706,647
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Original award $706,647
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Subawards

Subrecipient Amount Awarded
Regents Of The University Of Michigan The goal of the collaboration between Sub PIs at The University of Michigan and PI at Georgetown University is to define and rapidly translate the omics… $293,902
Regents Of The University Of Michigan The goal of the collaboration between Sub PIs at The University of Michigan and PI at Georgetown University is to define and rapidly translate the omics… $321,144
National And Kapodistrian University Of Athens Sub PI and the team at the University of Athens will provide samples (tissue, blood, buccal) from patients diagnosed with oral dysplasia and oral cancer… $99,926
National And Kapodistrian University Of Athens Statement of Work – University of Athens Dr. Gagari and the team at the University of Athens will provide samples (tissue, blood, buccal) from patients… $98,142

Quick answers

Who received award U01DE033348?

U01DE033348 was awarded to Georgetown University by National Institute of Dental and Craniofacial Research (National Institutes of Health) on September 1, 2023.

How much is award U01DE033348 worth?

$4,734,316 has been obligated on U01DE033348.

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