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- Title
The Somatic Nature of Cancer Allows It to Affect Highly Constrained Genes.
- Authors
Ostrow, Sheli L.; Hershberg, Ruth
- Abstract
Cancer is special among genetic disorders intwomajor ways:first, cancer is a disease of the most basicof cellular functions, such as cell proliferation, differentiation, and the maintenance of genomic integrity. Second, in contrast to most genetic disorders that are mediated by germline (hereditary)mutations, cancer is largely a somatic disease. Here we show that these two traits are not detached and that it is the somatic nature of cancer that allows it to affect themost basic of cellular functions. We begin by demonstrating that cancer genes are both more functionally central (as measured by their patterns of expression and protein interaction) and more evolutionarily constrained than non-cancer genetic disease genes. We then compare genes that are only modified somatically in cancer (hereinafter referred to as "somatic cancer genes") to those that can also be modified in a hereditary manner, contributing to cancer development (hereinafter referred to as "hereditary cancer genes").We show that both somatic and hereditary cancer genes are much more functionally central than genes contributing to non-cancer genetic disorders. At the same time, hereditary cancer genes are only as constrained as non-cancer hereditary disease genes,while somatic cancer genes tend to be much more constrained in evolution. Thus, it appears that it is the somatic nature of cancer that allows it to modify themost constrained genes and, therefore, affect the most basic of cellular functions.
- Subjects
CANCER; GENETIC disorders; SOMATIC cells; CELL proliferation; CELL differentiation; GERM cells; CELL populations
- Publication
Genome Biology & Evolution, 2016, Vol 8, Issue 5, p1614
- ISSN
1759-6653
- Publication type
Article
- DOI
10.1093/gbe/evw110