Evolution of oncogenic signatures of mutation hotspots in tyrosine kinases supports the atavistic hypothesis of cancer

Scientific Reports
Weiran ChenZhen Wang

Abstract

Cancer has been shown as an evolutionary process emerging hallmarks that are reminiscent of unicellular organisms. Since cancer is mostly driven by somatic mutations, especially by oncogenic hotspot mutations, we proposed a molecular atavism of cancer caused by gain-of-function mutations in oncogenes. As tyrosine kinase (TK) family contains the largest subgroup of oncogenes with hotspot mutations, we traced the most predominant mutation hotspots of TK oncogenes across phylogeny with the domain information and adjacent sequences integrated as onco-signatures. We detected 9 out of 17 TK oncogenes with onco-homologs possessing an onco-signature, which could be divided into two classes by whether their onco-homologs existed in mammals or not. In Class I we identified mammalian onco-homologs assuming oncogenic functions with onco-signatures always intact in cancer, such as HCK and LYN. In Class II with no bona fide mammalian onco-homologs, Pyk2, a protist onco-homolog with an onco-signature of BRAF was found assuming oncogenic-like functions. Onco-signatures in both classes root deep in the primitive system. Together, these evidences supported our proposal that cancer can be driven by reverse evolution of oncogenes through gain-of-f...Continue Reading

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Citations

Jul 18, 2020·Biochemical Society Transactions·Aurora M Nedelcu
Jan 16, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sabateeshan MathavarajahRobert J Huber
Aug 12, 2015·F1000Research·Brendon J Coventry, Maciej Henneberg
May 3, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Ping YangQuansheng Zhou

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Methods Mentioned

BETA
xenograft

Software Mentioned

phmmer
COSMIC
Clustal Omega
Blastp
HMMER

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