2023 World Conference on Lung Cancer (Posters)-P1.22. Molecular Profiling Reveals Distinct Clinical and Genomic Features as Potential Therapeutic Targets in Pulmonary Spindle Cell Carcinoma

P1.22. Molecular Profiling Reveals Distinct Clinical and Genomic Features as Potential Therapeutic Targets in Pulmonary Spindle Cell Carcinoma - PDF(Slides)

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Pulmonary spindle cell carcinoma (PSCC) is a rare and aggressive subtype of pulmonary sarcomatoid carcinoma (PSC) with poor prognosis. However, the molecular characteristics of PSCC are not well understood, making diagnosis and treatment optimization challenging. <br /><br />In this study, baseline tumors from 22 PSCC patients were analyzed using next-generation sequencing of 425 cancer-relevant genes. The study found that TP53, TERT, MET, CDKN2A/B, RB1, LRP1B, and FAT1 were the most frequently mutated genes in PSCC. Significant differences in the genomic landscape of PSCC were observed compared to PSC, including higher frequencies of ALK fusions and DNA repair-associated gene alterations in BRCA1/2. <br /><br />Additionally, actionable targets were identified in 81.8% of PSCC patients. The median tumor mutational burden (TMB) in PSCC was lower than in PSC and other non-small cell lung cancers (NSCLCs), but slightly higher than in other solid tumors. Altered RTK/RAS and DNA mismatch repair pathways were associated with higher TMB, while CDKN2A variants correlated with lower TMB. <br /><br />Furthermore, a prognostic model was constructed using mutational signature data obtained from baseline PSCC tumors, which showed a significant stratification effect in predicting overall survival of patients. <br /><br />The study also compared the effectiveness of baseline plasma circulating tumor DNA (ctDNA) to primary tumor tissues in detecting genetic variants. While ctDNA showed comparable effectiveness in detecting single nucleotide variants, it had a significantly lower detection rate for copy-number variants (CNVs). <br /><br />Overall, this study provides important insights into the molecular characteristics of PSCC and identifies potential therapeutic targets. The findings suggest that mutational signature data and plasma ctDNA analysis could be valuable tools for diagnosis and prognosis in PSCC patients.

Asset Subtitle

Yang Shao

Meta Tag

Speaker Yang Shao

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

Pulmonary spindle cell carcinoma

PSCC

molecular characteristics

diagnosis

treatment optimization

mutated genes

genomic landscape

tumor mutational burden

prognostic model

therapeutic targets