Genomic features and its potential implication in bone oligometastatic NSCLC

Abstract

Objectives: Emerging evidence have demonstrated that oligometastatic non-small cell lung cancer (NSCLC) can achieve clinical benefit from local consolidative therapy. Bone oligometastasis is common in advanced lung cancer, but little is known about its molecular features. The purpose of our study aimed to investigate the genomic landscape bone oligometastatic NSCLC. Methods: We collected paired blood and tissue samples from 31 bone oligometastatic NSCLC patients to make a comprehensive analysis of mutations by performing next-generation sequencing. Results: A total of 186 genomic mutations were detected from 105 distinct cancer-relevant genes, with a median number of 6 alterations per tumor. The most frequently mutated genes were EGFR (58%) and TP53 (55%), followed by KRAS (16%), CDKN2A (13%) and MET (13%). The signatures related to smoking, aging, homologous recombination deficiency and APOBEC were identified as the most important mutational processes in bone oligometastasis. The median tumor mutation burden was 4.4 mutations/Mb. Altogether, genetic alterations of bone oligometastasis are highly targetable that 74.19% of patients had at least one actionable alteration that was recommended for targeted therapy based on the OncoKB evidence. Of these patients, 16.13% had two actionable alterations that could potentially benefit from a different combination of targeted drugs to achieve better outcomes. Conclusion: Our research comprehensively elucidates the genomic features of bone oligometastatic NSCLC patients, which may optimize individualized cancer treatment in the era of precision medicine.