# Genetic Predictors of Ameloblastoma Behavior

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $464,469

## Abstract

PROJECT SUMMARY
Odontogenic tumors represent a spectrum of entities with differing morphologies, clinical presentations
and treatments, despite commonalities in association with tooth development and anatomy. The
complexity of this classification system is challenging for most pathologists, who rarely see these
tumors, and the treatment options are largely limited to the extent of surgery, which can result in
disfigurement, create functional problems with speech and swallowing, and is not always curative.
Recent studies suggest that there are recurrent genomic events in at least some of these tumors. We
have discovered activating mutations in SMO (most commonly SMO-L412F), part of the Hedgehog
pathway, and in the mitogen-activated protein kinase (MAPK) pathway (most commonly BRAF-V600E)
in over 80% of ameloblastomas. Others had previously found PTCH1 germline inactivation, also part of
the Hedgehog pathway, in keratocystic odontogenic tumors associated with Gorlin syndrome (nevoid
basal cell carcinoma syndrome). These pathways are druggable and we hypothesize that a new
paradigm for the diagnostic classification and treatment of odontogenic tumors can be generated with
genetic analysis.
We will conduct whole-exome sequencing and transcriptome sequencing of odontogenic tumors,
focusing on ameloblastoma, keratocystic odontogenic tumors and other morphologically-similar
diagnoses, to identify driver mutations and oncogenic pathways. Using both the mutation and
expression profiles, we will create a novel classification system for odontogenic neoplasms. We will
create multiple new ameloblastoma cell lines from patient material bearing recurrent driver mutations,
including BRAF, SMO, KRAS, and FGFR2. These new cell culture models will enable us to examine
the response to gene targeted therapies, as well as to anticipate likely mechanisms of therapy
resistance.

## Key facts

- **NIH application ID:** 9941074
- **Project number:** 5R01DE026502-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JONATHAN R POLLACK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,469
- **Award type:** 5
- **Project period:** 2017-07-12 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941074

## Citation

> US National Institutes of Health, RePORTER application 9941074, Genetic Predictors of Ameloblastoma Behavior (5R01DE026502-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9941074. Licensed CC0.

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