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Protein domain-based approaches for the identification and prioritization of therapeutically actionable cancer

Elisabetta Grillo1, Cosetta Ravelli1, Michela Corsini1

  • 1Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Biochimica Et Biophysica Acta. Reviews on Cancer
|August 17, 2021
PubMed

Insights

Protein domain-based analysis identifies functionally significant low-frequency cancer mutations missed by gene-centric methods. This approach aids in selecting targeted therapies for improved cancer patient management.

Area of Science:

  • Genomics
  • Computational Biology
  • Oncology

Background:

  • Next-generation sequencing (NGS) generates vast cancer variant data, necessitating computational methods for prioritizing mutations.
  • Current gene-centric approaches primarily identify high-frequency variants, potentially overlooking significant low-frequency mutations.

Purpose of the Study:

  • To introduce and explain protein domain (PD)-based strategies for prioritizing cancer mutations.
  • To discuss the potential of PD-based approaches in identifying functionally relevant low-frequency variants and guiding targeted therapy selection.

Main Methods:

  • Utilizing protein domain (PD)-based strategies to analyze recurrent mutations on analogous residues across homologous proteins.
  • Leveraging information transfer from known mutations to unknown ones within shared PDs.

Main Results:

  • PD-based approaches can identify functionally relevant low-frequency variants.
  • These strategies enable the transfer of knowledge regarding mutation effects and druggability.

Conclusions:

  • PD-based mutation prioritization can improve the selection of patient-specific targeted drugs.
  • This approach holds promise for enhancing the management of cancer patients by uncovering actionable mutations.
Keywords:
Cancer variantLow frequency mutationProtein domainSomatic mutation

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