Concordance Analysis of DNA and RNA Profiling: The MD Anderson IMPACT2 Study in Precision Oncology

Authors

Stephanie T Schmidt
Mehmet A Baysal
Siqing Fu
David S Hong
Sarina A Piha-Paul
Aung Naing
Jordi Rodon Ahnert
Timothy A Yap
Ecaterina Elena Dumbrava
Jennifer Beck
Funda Meric-Bernstam
Apostolia Maria Tsimberidou

Language

English

Publication Date

2-24-2026

Journal

Signal Transduction and Targeted Therapy

DOI

10.1038/s41392-026-02580-0

PMID

41730847

PMCID

PMC12929784

PubMedCentral® Posted Date

2-24-2026

PubMedCentral® Full Text Version

Post-print

Abstract

DNA profiling is an established method for cancer treatment selection, while RNA profiling remains investigational. We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival (OS) using patient data from IMPACT2 (NCT02152254), a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types. Molecular profiling, including DNA next-generation sequencing, was performed on all 829 patients in the IMPACT2 study. RNA profiling was performed by Tempus for 253 of 829 patients. We evaluated the concordance between DNA and RNA profiling, analyzed OS in 217 treated patients with RNA profiling, and assessed PD-L1 status and number of genes with altered expression. Fifty patients exhibited 58 concordant events, i.e., genomic and expression alteration(s) in the same gene, including 38 copy number events, and 41 patients had statistically significant concordance. We identified 123 gene pairs with significant associations between genomic and expression alterations (p < 0.05), including TP53 alterations with VEGFA overexpression. The median OS for patients with 0-2, 3-5, and ≥6 genes with altered expression was 9.8, 11.9, and 6.7 months, respectively (p = 0.03). These results underscore RNA profiling's potential actionability, and altered expression in ≥6 genes was associated with shorter OS. Significant concordance of TP53 alterations with VEGFA overexpression may partially explain tumor response to bevacizumab in TP53-mutant patients.

Keywords

Humans, Neoplasms, Female, Male, Precision Medicine, Middle Aged, Gene Expression Profiling, Aged, High-Throughput Nucleotide Sequencing, Gene Expression Regulation, Neoplastic, Adult, Translational research, Cancer genomics

Published Open-Access

yes

Recommended Citation

Schmidt, Stephanie T; Baysal, Mehmet A; Fu, Siqing; et al., "Concordance Analysis of DNA and RNA Profiling: The MD Anderson IMPACT2 Study in Precision Oncology" (2026). Faculty, Staff and Student Publications. 5848.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5848