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Comprehensive kinome NGS targeted expression profiling by KING-REX.

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  • 1NMS Oncology, Nerviano Medical Sciences Srl, Nerviano, MI, Italy.

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|April 25, 2019
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Summary
This summary is machine-generated.

We developed KING-REX, a cost-effective RNA sequencing panel for analyzing human kinase gene expression and detecting rearrangements. This tool aids in identifying novel kinase drug targets for cancer and other diseases.

Keywords:
Kinome gene expressionNGS RNA targeted panel

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Area of Science:

  • Biochemistry
  • Genomics
  • Molecular Biology

Background:

  • Protein kinases regulate cellular functions, and their dysregulation is implicated in human diseases.
  • Targeting kinases is a key strategy in drug development, but only a fraction of the human kinome is currently targeted.
  • There is a need for efficient methods to screen kinase expression for identifying new therapeutic targets.

Purpose of the Study:

  • To develop a comprehensive and cost-effective RNA-based assay for kinome-wide gene expression analysis.
  • To enable the detection of gene rearrangements in kinases through transcript imbalance analysis.
  • To facilitate the identification of novel kinase drug targets.

Main Methods:

  • Development of KING-REX (KINase Gene RNA EXpression), a targeted custom RNA assay panel for Next Generation Sequencing.
  • Design of a dedicated data analysis pipeline for 512 human kinases.
  • Implementation of paired assays for 319 kinases to detect 3'- and 5'-end transcript imbalances indicative of gene rearrangements.

Main Results:

  • KING-REX provides accurate gene expression assessment comparable to whole transcriptome analysis.
  • The assay robustly detects transcript portion imbalances in rearranged kinases, even in complex or degraded RNA samples.
  • Validation studies confirmed KING-REX's accuracy in cell line models with known gene fusions.

Conclusions:

  • KING-REX is a rapid and cost-effective tool for kinome investigation.
  • The assay supports kinase target identification in cancer biology and other human diseases.
  • KING-REX facilitates broader exploration of the kinome for therapeutic strategies.