Functional variomics and network perturbation: connecting genotype to phenotype in cancer

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• Proteins are integral to cellular networks, mediating signal transduction and biological functions.
• Genetic aberrations in cancer are increasingly understood to cause subtle, unique effects on protein function and network rewiring.
• These nuanced genetic alterations contribute to diverse phenotypic consequences observed across cancer patient populations.

Purpose of the Study:

• To review the current understanding of cancer genetic variants and their mechanistic effects on gene function within signalling networks.
• To highlight advanced computational and experimental strategies for analyzing mutation consequences at base-pair resolution.
• To establish a link between genotype and phenotype in cancer by understanding the pleiotropic effects of cancer genes.

Main Methods:

• Review of current literature on cancer genetic variants, mutation classes, and mechanistic effects.
• Discussion of computational and experimental strategies for studying mutation impacts.
• Analysis of signalling networks and their alterations due to genetic variations.

Main Results:

• Cancer genetic variants encompass a broad spectrum of mutation classes.
• Mutations can have diverse mechanistic effects on protein function and cellular signalling networks.
• Recent advances enable base-pair resolution studies of mutation consequences.

Conclusions:

• Understanding subtle, unique effects of genetic variants on protein function is crucial for cancer research.
• The pleiotropic effects of cancer genes can be elucidated by studying mutations at a granular level.
• Linking genotype to phenotype in cancer requires a detailed understanding of how genetic variants impact cellular networks.