Jun 4, 2015

Bringing Down Cancer Aircraft: Searching For Essential Hypomutated Proteins In Skin Melanoma

BioRxiv : the Preprint Server for Biology
Mikhail PyatnitskiySergei Moshkovskii

Abstract

Background We propose an approach to detection of essential proteins required for cancer cell survival. Gene is considered essential if mutation with high functional impact upon function of encoded protein causes death of cancer cell. We draw an analogy between essential cancer proteins and well-known Abraham Wald's work on estimating the plane critical areas using data on survivability of aircraft encountering enemy fire. Wald reasoned that parts hit least on the returned planes are critical and should be protected more. Similarly we propose that genes essential for tumor cell should carry less high-impact mutations in cancer compared to polymorphisms found in normal cells. Results We used data on mutations from the Cancer Genome Atlas and polymorphisms found in healthy humans (from 1000 Genomes Project) to predict 91 protein-coding genes essential for melanoma. These genes were selected according to several criteria including negative selection, expression in melanocytes and decrease in the proportion of high-impact mutations in cancer compared with normal cells. Gene ontology analysis revealed enrichment of essential proteins related to membrane and cell periphery. We speculate that this could be a sign of immune system-driv...Continue Reading

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Mentioned in this Paper

Gene Polymorphism
Study
Tumor Cells, Uncertain Whether Benign or Malignant
Immune System
Melanocyte
Interleukin 8A Receptor
Normal Cell
Signaling Cascade
Genome
Genes

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