2023 World Conference on Lung Cancer (Posters)-EP06.03. Genetic Characterization of Driving Metastasis in TP53-Mutant Non-small Cell Lung Cancer Patients

EP06.03. Genetic Characterization of Driving Metastasis in TP53-Mutant Non-small Cell Lung Cancer Patients - PDF(Abstract)

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The study presented in this session aimed to characterize the genetic features of driving metastasis in TP53-mutant non-small cell lung cancer (NSCLC) patients. The researchers assembled three cohorts of NSCLC patients who had previously undergone surgical resection, received first-line or second-line standard therapy. The correlation between genetic profiling and metastatic potential was analyzed in these cohorts. <br /><br />In stage I and stage II NSCLC patients, the frequency of TP53 mutations varied among different pathological subtypes, and the mutation burden increased with the frequency of TP53 mutations. TP53-mutant patients also harbored more driver genes. Low malignant subtypes had more EGFR gene mutations, while high malignant subtypes had more TP53 gene mutations. In lung adenocarcinoma (LUAD), the most common co-mutation was TP53 plus EGFR, while in lung squamous carcinoma (LUSC), the most common co-mutation was TP53 plus PIK3CA. <br /><br />In stage IV NSCLC patients who had previously received second-line or more therapy, TP53-mutant patients had a higher tumor mutation burden (TMB), but the high TMB did not necessarily mean more metastatic potential. Specific co-mutations, such as EGFR, KEAP1, ARID1A, ERBB2, and BRCA2, may contribute to increased metastatic potential in TP53-mutant patients. <br /><br />In stage IV NSCLC patients who had previously received first-line standard therapy, there was no correlation between TMB and metastases in TP53-mutant patients. However, the frequency of TP53 mutations was positively correlated with metastasis sites. Specific co-mutations, including EGFR, KEAP1, ARID1A, ERBB2, and BRCA2, were also associated with increased metastatic potential in TP53-mutant patients. <br /><br />Overall, this study provides a novel genetic landscape of metastatic spread in TP53-mutant NSCLC patients. These findings may contribute to the development of therapeutic strategies for this patient population.

Asset Subtitle

Jun Lu

Meta Tag

Speaker Jun Lu

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

metastasis

TP53-mutant

NSCLC

genetic profiling

mutation burden

driver genes

EGFR gene mutations

lung adenocarcinoma

LUAD

lung squamous carcinoma