# Clinicopathological Features of Non-Small Cell Lung Carcinoma with NRAS Mutation

## TL;DR

This study examines lung cancer cases with NRAS mutations and finds that mutations in codon 61 are linked to better survival outcomes.

## Contribution

The study identifies distinct clinicopathological features and prognosis differences based on NRAS mutation codons in lung cancer.

## Key findings

- NRAS mutations were found in 0.72% of non-small-cell lung carcinomas, mostly in codon 61.
- Patients with codon 61 NRAS mutations had significantly better survival than those with other mutations.
- Pleomorphic or sarcomatoid features were observed in 23.1% of NRAS-mutated lung cancer cases.

## Abstract

(1) Background: NRAS mutations affect fewer than 1% of lung adenocarcinomas. The aim of this study was to describe the clinicopathological features of lung carcinomas with NRAS mutations. (2) Methods: A series of NRAS-mutated lung carcinomas was collected from a molecular diagnostic unit (from four hospitals). The cases were analyzed with next-generation sequencing. A log-rank test for overall survival (OS) was calculated. (3) Results: NRAS mutations were detected in 14/1948 samples (0.72%) of non-small-cell lung carcinomas from 13 patients (8 males, 5 females). NRAS mutations involved codon 61 in the majority (9/13, 69.2%) of cases. The other NRAS mutations affected codon 12 (2/13, 15.4%), codon 13 (1/13, 7.7%), and codon 142 (1/13, 7.7%). In 7/13 cases, co-alterations in additional genes were also present. Pleomorphic/sarcomatoid features were identified in 3/13 (23.1%) cases, in 2/8 (25.0%) histological specimens, and in 2/5 (40.0%) surgical specimens, respectively. Follow-up data were available in 11/13 cases, with 6 patients deceased. By a log-rank test, patients with NRAS mutations in codon 61 had a better outcome (estimated mean of 32.6 ± 7.1 months) compared to those with other NRAS mutations (estimated mean of 8.7 ± 4.4 months), with a significant difference (p = 0.048 for OS). (4) Conclusions: Lung carcinomas with NRAS mutation may display pleomorphic or sarcomatoid features. Mutations in codon 61 showed a more favorable prognosis than those in other codons.