Clinical and genomic characterization of KRAS G13X non-small cell lung carcinoma

Benjamin J. Staum; Rachaita Lakra; Aditya Ravindra; Sarah L Mott; Deqin Ma; William Zeitler; Margaret Byrne; Nirmal Choradia; Abdul Rafeh Naqash; Raid Aljumaily; Muhammad Furqan

doi:10.3389/fonc.2026.1825959

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Clinical and genomic characterization of KRAS G13X non-small cell lung carcinoma

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Clinical and genomic characterization of KRAS G13X non-small cell lung carcinoma

Benjamin J. Staum, Rachaita Lakra, Aditya Ravindra, Sarah L Mott, Deqin Ma, William Zeitler, Margaret Byrne, Nirmal Choradia, Abdul Rafeh Naqash, Raid Aljumaily, …

Frontiers in oncology, Vol.16, 1825959

09/01/2026

DOI: 10.3389/fonc.2026.1825959

PMCID: PMC13581628

PMID: 42755510

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Abstract

Background KRAS mutations (KRASm)represent the most common oncogenic drivers in non–small cell lung cancer (NSCLC). However, molecular features and clinical implications of the less common, codon 13 mutations (KRAS G13X) remain poorly characterized. We conducted a retrospective study to characterize KRAS G13X-positive NSCLC. Methods We reviewed patients’ charts with KRASm NSCLC treated at University of Iowa Health Care. Based on intent of therapy, patients were assigned to curative-intent (CI) or palliative-intent (PI) cohorts. Clinicopathologic data, co-mutation profiles, and outcomes were assessed.Results A total of 108 CI and 100 PI patients were included. KRAS G13X accounted for 10% of KRASm NSCLC. KRAS G13X tumors were enriched for STK11, KEAP1, NFE2L2, and TSC1/2 co-mutations. In the CI cohort, KRAS G13X had the lowest 12-month disease-free survival (DFS) (41%), though KRAS subtype was not independently prognostic. Poor performance status, stage III disease, delayed treatment initiation, and not having ATM co-mutations were associated with inferior DFS. TET2 alterations were associated with worse overall survival (OS). In the PI cohort, KRAS G13X had the lowest 12-month progression-free survival (PFS) (17%) and OS (27%) compared to other KRAS alterations. On multivariable analysis, STK11, TERT, and TSC1/2 alterations remained independently associated with worse survival, while KRAS G13X and G12D tended to exhibit poorer OS. Conclusions KRAS G13X mutations represent a small but clinically meaningful subset of NSCLC defined by a distinctive co-mutation pattern. Outcomes appear driven predominantly by co-mutations. Combinational therapeutic strategies addressing these vulnerabilities can help improve outcomes.

clinical characterization

co-mutations

KRAS G13

molecular characterization

NSCLC

Details

Title: Subtitle: Clinical and genomic characterization of KRAS G13X non-small cell lung carcinoma
Creators: Benjamin J. Staum - Regions Hospital
Rachaita Lakra - University of Iowa
Aditya Ravindra - University of Iowa
Sarah L Mott - University of Iowa
Deqin Ma - University of Iowa
William Zeitler - University of Iowa
Margaret Byrne - University of Iowa
Nirmal Choradia - University of Oklahoma Health Sciences Center
Abdul Rafeh Naqash - University of Oklahoma Health Sciences Center
Raid Aljumaily - University of Oklahoma Health Sciences Center
Muhammad Furqan - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in oncology, Vol.16, 1825959
DOI: 10.3389/fonc.2026.1825959
PMID: 42755510
PMCID: PMC13581628
NLM abbreviation: Front Oncol
ISSN: 2234-943X
eISSN: 2234-943X
Publisher: Frontiers Media S.A
Language: English
Date published: 09/01/2026
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9985222684002771

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