Identifying pathways affected by cancer mutations

Area of Science:

• Genomics and Bioinformatics
• Cancer Biology
• Systems Biology

Background:

• Cancer is driven by genetic mutations affecting cellular processes.
• Understanding which biological pathways are impacted by these mutations is crucial for deciphering cancer mechanisms.
• Existing research often focuses on well-known pathways, potentially overlooking others.

Purpose of the Study:

• To identify and visualize pathways affected by cancer mutations across various cancer types.
• To investigate the relative impact of mutations on different pathway groups, including organismal systems.
• To uncover insights into fundamental cancer processes by analyzing commonly affected pathways.

Main Methods:

• Utilized mutation data from the COSMIC Whole Genomes database for 15 cancers.
• Integrated 297 human pathways from the KEGG pathway database, grouped by function.
• Defined recurrently mutated genes and pathways affected by these mutations.
• Developed novel doughnut plots for visualizing pathway and gene targeting in each cancer.

Main Results:

• The 'organismal systems' pathway group was found to be the most targeted by cancer mutations.
• This group showed greater targeting than established pathways like signal transduction, cell-cycle, apoptosis, and DNA repair.
• Analysis of pathways affected in ≥7 cancers provided insights into common cancer processes.

Conclusions:

• Organismal systems pathways play a significant, yet under-recognized, role in cancer development.
• Novel visualization techniques effectively illustrate the landscape of pathway involvement in cancer.
• Further research into organismal systems pathways is warranted to better understand and target cancer.