Highlights
- •Rural non-small cell lung cancer (NSCLC) patients have worse survival.
- •Whole exome sequencing reveals similar somatic mutation profile as urban patients.
- •Most common mutations and actionable genes are also observed in rural NSCLC.
- •24% of patients had variants in actionable genes based on OncoKB annotation.
- •Findings establish foundation for targeted clinical trials in rural NSCLC patients.
Abstract
Rural non-small cell lung cancer (NSCLC) patients do worse, largely related to lack
of access to care. In this study, the mutational characteristics and potential for
targeted therapy in rural, resectable NSCLC patients using whole exome sequencing
(WES) were analyzed. WES was performed on tumor-adjacent normal pairs from rural patients
undergoing resection for NSCLC. Sequencing alignment, variant-calling, annotation,
and tumor mutational burden (TMB) calculations were performed using standard methods.
cBioportal and OncoKB were used for comparisons of mutational frequencies and actionable
targets. Thirty-four NSCLC patients underwent WES after surgical resection. The gene
most frequently containing somatic variants was TP53. The median number of somatic variants was 188 (Range 11–1056), and median TMB was
3.30 (0.33–18.56) nonsynonymous mutations per Mb. Tumor stage and survival were not
associated with number of variants, TMB or TP53 mutational status. Significant concordance among the most common mutations when cross-referenced
to cBioportal (R = 0.78, p < 0.0001) was observed. 24% of patients had variants in actionable genes based on
OncoKB annotation. In summary, we demonstrate baseline mutational frequency and establish
foundations for targeted adjuvant trials in rural NSCLC patients with specific differences.
Future studies must ensure to include rural patients to improve NSCLC patient outcomes.
Keywords
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Article info
Publication history
Published online: September 23, 2022
Accepted:
September 19,
2022
Received in revised form:
June 30,
2022
Received:
April 15,
2022
Identification
Copyright
Published by Elsevier Inc.
