RT Journal Article
SR Electronic
T1 Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 333633
DO 10.1101/333633
A1 Anqi Jing
A1 Frederick S. Vizeacoumar
A1 Sreejit Parameswaran
A1 Bjorn Haave
A1 Chelsea E. Cunningham
A1 Yuliang Wu
A1 Roland Arnold
A1 Keith Bonham
A1 Andrew Freywald
A1 Jie Han
A1 Franco J. Vizeacoumar
YR 2018
UL http://biorxiv.org/content/early/2018/05/29/333633.abstract
AB Can transcriptomic alterations drive the evolution of tumors? We rationalize that expressional changes found in all patients arise earlier in tumor development compared to alterations that occur only in limited subsets of patients. Our analyses of non-mutated genes from the non-amplified regions of the genome of 158 triple negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC. Phylogenetic analyses of these genes predict a “punctuated burst” of multiple gene up-regulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression. Remarkably, this punctuated burst of expressional changes is instigated by hypoxia-related molecular events, predominantly in two groups of genes that control chromosomal instability (CIN) and remodel tumor microenvironment (TME). We conclude that alterations in the transcriptome are not stochastic and that early stage hypoxia induces CIN and TME remodeling to permit further tumor evolution.List of AbbreviationsCINchromosomal instabilityTNBCtriple negative breast cancerTCGAThe Cancer Genome AtlasCNVcopy number variation