# Elucidating the Role of MALAT1 Somatic Driver Mutations in Colorectal Cancer

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $387,731

## Abstract

Tumorigenesis and cancer progression are caused by the accumulation of mutations in driver genes. Distinct
combinations of driver gene mutations cooperate during tumor evolution, revealed by increased frequency of
mutation co-occurrence from evolutionary selection. Recently, long noncoding RNAs (lncRNAs) have been
shown to be cancer driver genes. Here we identified MALAT1 as a novel colorectal cancer (CRC) driver.
MALAT1 CRC mutations are enriched in competing endogenous (ceRNA)-microRNA binding sites, and CRCs
carrying MALAT1 mutations are specifically enriched for BRAF mutations. This is the first systematically
identified example of cooperation between coding and lncRNA cancer driver genes. Here, we will test the
hypothesis that MALAT1 competing endogenous RNA mutations drive colon tumorigenesis, and also test
hypotheses that MALAT1 mutations promote CRC growth and BRAF inhibitor resistance. Our work will provide
unprecedented detail into the precise mechanistic roles of MALAT1 and MALAT1/BRAF mutations, and has
potential impact to drive clinical precision medicine sequencing panel studies of MALAT1/BRAF mutations in
EGFR inhibitor therapy resistance, serrated CRC prognosis, and BRAF/EGFR inhibitor combination therapy
clinical trials.

## Key facts

- **NIH application ID:** 9831623
- **Project number:** 5R01CA227722-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Steven M Lipkin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,731
- **Award type:** 5
- **Project period:** 2018-12-04 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831623

## Citation

> US National Institutes of Health, RePORTER application 9831623, Elucidating the Role of MALAT1 Somatic Driver Mutations in Colorectal Cancer (5R01CA227722-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9831623. Licensed CC0.

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