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Retrospective analysis of FFPE based Wilms' Tumor samples through copy number and somatic mutation related Molecular

Neetu Singh1, Dinesh K Sahu2, Madhumati Goel3

  • 1Advanced Molecular Science Research Center (Center for Advanced Research), King George's Medical University, Lucknow 226 003, India.

Gene
|April 28, 2015
PubMed
Summary

This study analyzed copy number and loss of heterozygosity in Wilms' Tumor (WT) samples. Key genetic alterations and affected pathways were identified, potentially aiding in disease diagnosis and prognosis.

Keywords:
Copy number variationLOHOncogeneOncoscan arrayTumor-suppressor genesWilms' Tumor

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Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Wilms' Tumor (WT) is a pediatric kidney cancer with complex genetic underpinnings.
  • Understanding copy number (CN) and loss of heterozygosity (LOH) patterns is crucial for WT research.
  • Previous studies have identified specific genetic alterations in WT, but comprehensive profiling is ongoing.

Purpose of the Study:

  • To retrospectively analyze CN and LOH imbalances in histopathologically characterized WT samples.
  • To identify specific genetic gains and losses associated with WT.
  • To investigate the impact of these genetic alterations on major cellular pathways.

Main Methods:

  • Analysis of fifteen formalin-fixed paraffin-embedded (FFPE) Wilms' Tumor samples.
  • Utilized Molecular-Inversion-Probe based-Oncoscan Array for DNA analysis.
  • Employed Nexus-Express OncoScan software for data analysis.

Main Results:

  • Identified specific gains (e.g., 3p, 4p, 7, 12p-q) and losses (e.g., 1p, 11p-q, 21q, 22q) in WT samples.
  • Observed maximum LOH in Chromosome 11, consistent with prior research, and novel LOH regions in Chromosome 7.
  • Detected alterations in key pathways including RAS, PI3K, NOTCH/TGF-β, Cell Cycle, and Apoptosis.

Conclusions:

  • The comprehensive genetic profiling of WT samples reveals significant CN and LOH alterations.
  • Identified genetic imbalances impact critical oncogenic and tumor-suppressor pathways.
  • These findings may contribute to improved diagnosis and prognosis of Wilms' Tumor upon further validation.