Functional variomics and network perturbation: connecting genotype to phenotype in cancer.
Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants, including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signalling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Song
S
Yi
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Shengda
S
Lin
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Yongsheng
Y
Li
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Wei
W
Zhao
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Gordon B
GB
Mills
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
Nidhi
N
Sahni
D053263:Gene Regulatory Networks; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053858:Metabolic Networks and Pathways; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D060066:Protein Interaction Maps