WCLC 2025 - Posters & ePosters-P3.13.23 Copy Number Gain of MYC-Paralogs Represents Proliferative Phenotype and Poor Prognosis in Resected Small Cell Lung Cancer

P3.13.23 Copy Number Gain of MYC-Paralogs Represents Proliferative Phenotype and Poor Prognosis in Resected Small Cell Lung Cancer

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This study developed a novel triple-probe fluorescence in situ hybridization (triple-FISH) technique targeting the MYC paralogs—MYC, MYCL, and MYCN—to detect copy number gains (CNGs) in surgically resected small cell lung cancer (SCLC) samples. Traditional single-probe FISH and immunohistochemistry (IHC) methods tend to miss low-level variations, whereas this triple-FISH approach identifies CNG when any MYC paralog shows over 3 signals per cell.<br /><br />In a cohort of 56 resected SCLC samples, 30 exhibited MYC-paralog CNGs: 10 cases with MYC, 18 with MYCL, and 2 with MYCN amplification. These CNGs were validated by whole genome sequencing. Furthermore, multiplex immunohistochemical profiling using a six-antibody panel (including Ki67, a proliferation marker) revealed a significant association between MYC-paralog CNG and elevated tumor proliferation.<br /><br />Survival analyses demonstrated that the presence of MYC-paralog CNG correlates with poor prognosis in resected SCLC patients. Spatial analysis of the tumor microenvironment indicated that tumors harboring these CNGs exhibited proliferative phenotypes characterized by higher Ki67 tumor infiltration. <br /><br />While the study establishes the clinical importance of MYC-paralog CNG as a marker of aggressive tumor behavior and worse outcomes, the underlying biological mechanisms remain unclear, including possible roles in chemoresistance, immune evasion, and brain metastasis. Future research is suggested to explore targeted therapies against MYC paralogs to potentially reverse the proliferative phenotype, improve prognosis, and enhance precision diagnosis and treatment of SCLC.<br /><br />In summary, this work introduces a robust triple-FISH method to detect clinically relevant MYC-paralog amplifications in SCLC, linking these genetic alterations to tumor proliferation and poor patient survival, and highlights their potential as therapeutic targets in this aggressive lung cancer subtype.

Asset Subtitle

Yan Ju

Meta Tag

Speaker Yan Ju

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

triple-FISH

MYC paralogs

copy number gains

small cell lung cancer

MYC amplification

immunohistochemistry

tumor proliferation

Ki67 marker

poor prognosis

targeted therapy