2023 World Conference on Lung Cancer (Posters)-EP08.03. Copy Number Variants and Late Somatic Mutations Underlying Tumor Progression in NADIM Clinical Trials

EP08.03. Copy Number Variants and Late Somatic Mutations Underlying Tumor Progression in NADIM Clinical Trials - PDF(Slides)

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This study examines the molecular mechanisms underlying disease progression in patients with locally-advanced non-small-cell lung cancer (NSCLC) who were treated with neoadjuvant chemoimmunotherapy. The study focuses on copy number variants (CNVs) and late somatic mutations as potential drivers of tumor progression. Plasma samples from patients in the NADIM and NADIM II cohorts were analyzed.<br /><br />The results show that somatic CNVs in genes such as RET, EGFR, and FGFR were acquired in plasma samples collected during disease progression in patients treated with neoadjuvant chemoimmunotherapy. These CNVs may have important implications for subsequent treatment selection.<br /><br />The study included 57 patients from the NADIM cohort and 6 patients from the NADIM II cohort. Somatic variants were detected in 87.5% of the samples, indicating a high degree of molecular heterogeneity. A total of 90 genes were found to be mutated, with 32.2% of the mutated genes overlapping across different samples. The most frequently mutated genes were TP53, SETBP1, and GRIN2A.<br /><br />In terms of variant types, deletions were the most common (50.7%), followed by missense mutations (40.4%), insertions (4.4%), copy number variations (2.9%), and multiple nucleotide variants (1.5%). The study also identified several copy number variants, including RET amplification alongside EGFR amplification, FGFR3 amplification, and RET amplification.<br /><br />Furthermore, loss of function somatic mutations were detected in tumor suppressor genes such as TP53, STK11, and RNF43.<br /><br />In conclusion, this study highlights the role of CNVs and late somatic mutations in tumor progression in NSCLC patients treated with neoadjuvant chemoimmunotherapy. The findings suggest that these molecular alterations may influence treatment outcomes and should be considered in treatment selection. Further research is needed to validate these findings and explore their clinical implications.

Asset Subtitle

Roberto Serna Blasco

Meta Tag

Speaker Roberto Serna Blasco

Topic Local-Regional NSCLC: Novel Therapies & Trials

Keywords

molecular mechanisms

disease progression

NSCLC

neoadjuvant chemoimmunotherapy

copy number variants

tumor progression

plasma samples

molecular heterogeneity

tumor suppressor genes

treatment outcomes