Phylostratigraphic analysis of tumor and developmental transcriptomes reveals relationship between oncogenesis, phylogenesis and ontogenesis
- 23 February 2018
- journal article
- research article
- Published by IOP Publishing in Convergent Science Physical Oncology
- Vol. 4 (2), 025002
- https://doi.org/10.1088/2057-1739/aab1b0
Abstract
The question of the existence of cancer is inadequately answered by invoking somatic mutations or the disruptions of cellular and tissue control mechanisms. As such uniformly random events alone cannot account for the almost inevitable occurrence of an extremely complex process such as cancer. In the different epistemic realm, an ultimate explanation of cancer is that cancer is a reversion of a cell to an ancestral pre-Metazoan state, i.e. a cellular form of atavism. Several studies have suggested that genes involved in cancer have evolved at particular evolutionary time linked to the unicellular-multicellular transition. Here we used a refined phylostratigraphic analysis of evolutionary ages of the known genes/pathways associated with cancer and the genes differentially expressed between normal and cancer tissue as well as between embryonic and mature (differentiated) cells. We found that cancer-specific transcriptomes and cancer-related pathways were enriched for genes that evolved in the pre-Metazoan era and depleted of genes that evolved in the post-Metazoan era. By contrast an opposite relation was found for cell maturation: the age distribution frequency of the genes expressed in differentiated epithelial cells were enriched for post-Metazoan genes and depleted of pre-Metazoan ones. These findings support the atavism theory that cancer cells manifest the reactivation of an ancient ancestral state featuring unicellular modalities. Thus our bioinformatics analyses suggest that not only does oncogenesis recapitulate ontogenesis, and ontogenesis recapitulates phylogenesis, but also oncogenesis recapitulates phylogenesis. This more encompassing perspective may offer a natural organizing framework for genetic alterations in cancers and point to new treatment options that target the genes controlling the atavism transition.Keywords
Funding Information
- National Science Foundation (PHY11-25915)
- Foundation for the National Institutes of Health (U54CA143682)
- National Institute of General Medical Sciences (2P50GM076547-06A1, R01GM109964)
This publication has 80 references indexed in Scilit:
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16BNature Medicine, 2012
- Clonal evolution in cancerNature, 2012
- How Cancer Shapes Evolution and How Evolution Shapes CancerEvolution: Education and Outreach, 2011
- Peto's Paradox: evolution's prescription for cancer preventionTrends in Ecology & Evolution, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- DNA Damage-Mediated Induction of a Chemoresistant NicheCell, 2010
- Theories of carcinogenesis: An emerging perspectiveSeminars in Cancer Biology, 2008
- Integrative analysis of the cancer transcriptomeNature Genetics, 2005
- The Hallmarks of CancerCell, 2000