# Concordance analysis of DNA and RNA profiling: The MD Anderson IMPACT2 study in precision oncology

## TL;DR

This study compares DNA and RNA profiling in cancer patients, finding that RNA profiling can provide actionable insights and may influence survival outcomes.

## Contribution

The study identifies significant concordance between DNA and RNA alterations and links altered gene expression to survival differences in cancer patients.

## Key findings

- 58 concordant events were found between DNA and RNA alterations in the same gene.
- Patients with ≥6 genes showing altered expression had shorter overall survival (6.7 months) compared to those with fewer altered genes.
- TP53 alterations were significantly associated with VEGFA overexpression, potentially explaining responses to bevacizumab.

## 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.