2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - Posters-PP01.05: Integrative single-cell tracking of genome evolution and tumor cell plasticity in Small Cell Lung Cancer (SCLC)

PP01.05: Integrative single-cell tracking of genome evolution and tumor cell plasticity in Small Cell Lung Cancer (SCLC)

Back to course

Pdf Summary

The document discusses significant findings in small cell lung cancer (SCLC) research, primarily focusing on the genetic and molecular dynamics of SCLC tumors. The research was presented at the IASCL Hot Topic Meeting in New York and involves contributions from a team based at the University of Cologne.

Key highlights from the study include:

1. <strong>Nature of SCLC</strong>: SCLC is a neuroendocrine tumor responsible for about 20% of lung cancer cases, characterized by rapid onset therapy resistance and poor outcomes. It often involves the near-universal loss of TP53 and RB1 genes.

2. <strong>Transcriptional Heterogeneity</strong>: The study emphasizes the heterogeneity of SCLC at the transcriptional level. A classification system based on four lineage transcription factors (ASCL1, NEUROD1, POU2F3, and YAP1) has been proposed to better understand these variations.

3. <strong>Comprehensive Analysis Using scRNA Sequencing</strong>: The study sequenced transcriptomes from over 220,000 single SCLC cells across 56 tumors from 42 patients. It involved scRNA sequencing of tumors derived both from direct patient materials and xenograft models.

4. <strong>Co-expression of Lineage Transcription Factors</strong>: Findings indicate that different lineage transcription factors are co-expressed within individual tumors, suggesting a concerted regulatory mechanism in SCLC.

5. <strong>Plasticity and Clonal Evolution</strong>: RNA-velocity analysis showed significant plasticity related to TF-subgroups within individual tumors. The study also examined cell-cell interactions and intermetastatic heterogeneity, revealing recurrent pathways and NOTCH interaction patterns.

6. <strong>Immune Cell Profiling</strong>: Detailed immune cell analysis was performed, uncovering significant diversity within the tumor microenvironment, with various immune cells present.

Overall, this research provides insight into the complex genetic makeup and evolution of SCLC, potentially guiding more effective treatment approaches and classifications based on molecular signatures.

Asset Subtitle

Marcel Schmiel

Keywords

small cell lung cancer

SCLC

genetic dynamics

molecular dynamics

TP53

RB1

transcriptional heterogeneity

scRNA sequencing

lineage transcription factors

immune cell profiling