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Transcriptional background effects on a tumor driver gene in different pigment cell types of medaka

Shahad Abdulsahib1, William Boswell1, Mikki Boswell1

  • 1Department of Chemistry and Biochemistry, Xiphophorus Genetic Stock Center, Texas State University, San Marcos, Texas, USA.

Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
|October 25, 2023
PubMed

Insights

The Xiphophorus melanoma receptor kinase (xmrk) oncogene drives diverse fish tumors. Transcriptomic analysis reveals distinct molecular pathways in melanoma versus xanthoerythrophoroma, influencing tumor development and outcomes.

Area of Science:

  • * Molecular oncology
  • * Comparative genomics
  • * Cancer research

Background:

  • * The Xiphophorus melanoma receptor kinase (xmrk) gene is a known oncogene driving melanocyte tumors in Xiphophorus fish.
  • * Ectopic expression of xmrk in medaka fish induces various pigment cell tumor types, suggesting a transcriptomic background effect on oncogenesis.
  • * While xmrk's role in melanomagenesis is understood, the genetic modifiers of its oncogenic effects remain uninvestigated.

Purpose of the Study:

  • * To investigate the genetic networks underlying different tumor histologies driven by the xmrk oncogene.
  • * To compare the transcriptional profiles of melanoma and xanthoerythrophoroma tumors arising in the same xmrk transgenic medaka.
  • * To identify co-expressed genes and differentially expressed genes associated with xmrk in these distinct tumor types.

Main Methods:

  • * Isolation of melanoma and xanthoerythrophoroma tumors from individual xmrk transgenic medaka.
  • * Establishment and comparison of transcriptional profiles for both tumor types.
  • * Analysis of gene co-expression with xmrk and differential gene expression between tumor types.

Main Results:

  • * Melanoma and xanthoerythrophoroma tumors exhibit distinct transcriptional signatures, reflecting varied molecular interactions with the xmrk oncogene.
  • * Melanoma tumors show gene expression patterns associated with proliferation and invasion.
  • * Xanthoerythrophoroma tumors display gene expression profiles related to metabolism and DNA repair.

Conclusions:

  • * Transcriptomic backgrounds, influenced by cell-type-specific gene expression downstream of xmrk signaling, significantly modulate tumor development.
  • * These distinct transcriptomic landscapes contribute to varied tumor progression and outcomes.
  • * Understanding these genetic networks provides insights into the multifaceted oncogenic activity of xmrk.
Keywords:
disease modifiergenetic backgroundmedakamelanoma

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