# Mutations and Target Genes in Adenoid Cystic Carcinoma

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $359,813

## Abstract

Project Summary/Abstract
 Adenoid Cystic Carcinoma (ACC) is the second most frequent malignancy of the minor and major salivary
glands and has poor long-term prognosis. Molecular studies of ACC tumors have been complicated by the
relative rarity of the tumors, differences in diagnosis and characterization, and the lack of bona fide ACC cell
lines. A large majority of ACC tumors contain a recurrent t(6;9) translocation which fuses the MYB proto-
oncogene on chromosome 6q to the NFIB gene on chromosome 9p. The translocations have multiple effects:
leading to the expression of truncated, oncogenic forms of the c-Myb transcription factor and juxtaposing the
MYB gene next to tissue specific enhancers that lead to overexpression in ACC tumors. The major challenge
in studying ACC tumors has been the need to perform detailed molecular characterizations on rare tumor
samples that are old enough to have clinical outcome information. To address that challenge, we developed
and optimized innovative RNA-seq methods to analyze RNA derived from archival Formaldehyde-Fixed,
Paraffin-Embedded (FFPE) ACC tumor samples, which allowed us to perform in-depth transcriptome analyses
on these rare tumor samples. Our efforts led to the identification of novel, recurrent fusions involving both MYB
and the related MYBL1 oncogene, which encodes the A-Myb transcription factor. We uncovered new insights
into the mechanisms of activation of these genes in ACC tumors and characterized the gene expression
profiles of ACC tumors and how they are related to MYB and MYBL1 oncogene expression. These findings put
us in a unique position to investigate the mechanisms leading to ACC tumors and to identify the important
regulators and potential therapeutic targets in ACC tumors. Our results lead us to hypothesize that salivary
gland ACC tumors are caused by mutated MYB or MYBL1 oncogenes overexpressed due to regulation by
tissue-specific enhancers, resulting in the induction of a characteristic, ACC-specific gene expression program.
In this revised renewal application, we will build on the studies that we have completed and make use of the
extensive RNA-seq data that we have generated for ACC tumor samples. We will focus on performing
extensive and in-depth bioinformatics analyses of the RNA-seq data and on performing molecular validations
to gain insights into the mechanisms that lead to ACC tumors. We will also investigate the mechanisms that
lead to overexpression of the MYB and MYBL1 oncogenes in ACC tumors, with the goal of identifying new
therapeutic targets. We have assembled an interactive team of investigators with expertise in molecular
biology, genomics, bioinformatics, biostatistics and computational methods who will focus on these aims to
answer key questions about the biology of these devastating tumors.

## Key facts

- **NIH application ID:** 10217096
- **Project number:** 5R01DE023222-09
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** SCOTT A. NESS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,813
- **Award type:** 5
- **Project period:** 2012-09-10 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217096

## Citation

> US National Institutes of Health, RePORTER application 10217096, Mutations and Target Genes in Adenoid Cystic Carcinoma (5R01DE023222-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217096. Licensed CC0.

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