AI Article Synopsis
- Combined small-cell lung cancer (cSCLC) is a unique form that includes both small-cell and non-small-cell lung cancer, but the genetic differences between these components in cSCLC and metachronously transformed SCLC (mtSCLC) are not well understood.
- The study examined four cSCLC cases and one mtSCLC case using advanced genetic testing methods to identify mutations and gene expression levels of specific neuroendocrine transcription factors.
- The findings indicated that while both SCLC and NSCLC components shared common mutations (like in TP53), the SCLC component had significantly higher ASCL1 expression, suggesting that the evolution of these cancer types may relate more to differences in gene expression rather than mutations.
Article Abstract
Background: Combined small-cell lung cancer (cSCLC) is a rare type of small-cell lung cancer (SCLC) that includes both SCLC and non-small-cell lung cancer (NSCLC). The molecular biological mechanisms underlying the heterogeneity of histological types in combined or metachronously transformed SCLC (mtSCLC) remain unclear. This study aimed to investigate the relationship between genetic alterations and each histological component heterogeneously detected in cSCLC and mtSCLC.
Methods: This study included four cSCLC cases and one mtSCLC case. Formalin-fixed and paraffin-embedded sections of each histological component of these tumors were subjected to next-generation sequencing (NGS) and quantitative reverse transcription-polymerase chain reaction to investigate the genetic mutations and expression levels of neuroendocrine cell-specific transcription factors (achaete-scute homolog-1 [ASCL1], brain-2 [BRN2] also known as POU domain class 3 transcription factor 2, nuclear factor 1 B [NF1B], insulinoma-associated protein 1 [INSM1], and thyroid transcription factor-1 [TTF-1]).
Results: NGS analysis revealed that SCLC and NSCLC components share the same somatic mutations detected most frequently in TP53, and also in RB1 and EGFR. Gene expression analysis showed ASCL1 expression was significantly lower in the NSCLC component than in the SCLC component.
Conclusion: We conclude that the morphological evolution of heterogeneous histological components in cSCLC may be associated with differences in ASCL1 expression levels, but not in acquired somatic gene mutations.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376179 | PMC |
| http://dx.doi.org/10.1111/1759-7714.14574 | DOI Listing |
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