Insights into treatment-specific prognostic somatic mutations in NSCLC from the AACR NSCLC GENIE BPC cohort analysis

TL;DR

This study identifies genetic markers linked to treatment responses in lung cancer patients, helping guide personalized therapy choices.

Contribution

The study introduces treatment-specific mutation signatures for chemotherapy and immunotherapy in NSCLC patients.

Findings

Somatic mutation signatures were found to correlate with responses to immunotherapy and chemotherapy.

EGFR mutation status significantly influences the predictive power of chemotherapy-associated signatures.

An EGFR wild-type-specific mutation signature was developed for chemotherapy selection.

Abstract

Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible.

To investigate the association between a patient’s responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients.

We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection.

Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

The online version contains supplementary material available at 10.1186/s12890-024-03124-4.

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