# Mutations and Target Genes in Adenoid Cystic Carcinoma

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $428,710

## Abstract

Project Summary/Abstract
 Adenoid Cystic Carcinoma (ACC) is the second most common type of salivary gland tumor, but can also
arise in other tissues such as lacrimal gland, breast and skin. ACC tumors display heterogeneous morphology
and have a variable clinical course. Many ACC patients survive 10 years or more after the standard therapy of
surgery and radiation, but a fraction succumb much more quickly and others acquire distant metastases or
relapse 5 or more years after the initial treatment. So patients often have to endure significant morbidity
including reconstructive surgery while living under the threat of recurrence for decades.
 ACC is one of the only human tumors in which mutations involving the MYB oncogene are known to be the
most common driver. A large fraction of ACC tumors harbor a t(6;9) translocation, which juxtaposes an
enhancer from the NFIB gene on chromosome 9p close to the MYB oncogene on chromosome 6q. However,
ACC tumors have heterogeneous molecular characteristics. About half the tumors that express MYB harbor
translocations that fuse the MYB and NFIB genes, resulting in a ‘broken’ or truncated MYB gene that can only
express Myb proteins with C-terminal truncations – mutations that are known to activate the oncogenic
potential of the Myb transcription factor. But the remaining MYB positive tumors appear to express full-length
Myb proteins without any fusion to NFIB. And some tumors harbor different translocations that position the
MYB gene close to other enhancers or that involve the related MYBL1 gene instead of MYB. This molecular
heterogeneity is also reflected in the subgroups of ACC patients that have been identified by gene expression
profiling, including at least one poor-prognosis subgroup with a unique gene expression profile and another
subgroup that expresses neither MYB nor MYBL1 and must harbor as yet unidentified driver mutations.
 Deciphering the molecular events that lead to ACC has been complicated by the lack of adequate cell
models for this tumor. To avoid any issues from highly selected or mislabeled cell lines, our strategy has been
to utilize primary salivary gland ACC patient samples, an approach that has led to numerous important results
that have reshaped our understanding of ACC tumors. In this competing renewal application we will generate
the largest set of ACC tumor RNA-seq data in order to move the field forward in several ways. We will address
the heterogeneity of ACC tumors and patients, set the stage for the development of new therapeutic strategies
that target Myb proteins, use patient samples in a translational way to validate experimental results about Myb
protein biology and we will begin migrating our approaches to clinical (CLIA) laboratories to make them usable
in the clinic.

## Key facts

- **NIH application ID:** 10807057
- **Project number:** 5R01DE023222-11
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Viswanathan Palanisamy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $428,710
- **Award type:** 5
- **Project period:** 2012-09-10 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807057

## Citation

> US National Institutes of Health, RePORTER application 10807057, Mutations and Target Genes in Adenoid Cystic Carcinoma (5R01DE023222-11). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10807057. Licensed CC0.

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