TY - JOUR
T1 - Transcriptomic Heterogeneity in Cancer as a Consequence of Dysregulation of the Gene-Gene Interaction Network
AU - van Wieringen, W.N.
AU - van der Vaart, A.W.
PY - 2015
Y1 - 2015
N2 - Many pathways are dysregulated in cancer. Dysregulation of the regulatory network results in less control of transcript levels in the cell. Hence, dysregulation is reflected in the heterogeneity of the transcriptome: the more dysregulated the pathway, the more the transcriptomic heterogeneity. We identify four scenarios for a transcriptomic heterogeneity increase (i.e., pathway dysregulation) in cancer: (1) activation of a molecular switch, (2) a structural change in a regulator, (3) a temporal change in a regulator, and (4) weakening of gene–gene interactions. These mechanisms are statistically motivated, explored in silico, and their plausibility to occur in vivo illustrated by means of oncogenomics data of breast cancer studies.
AB - Many pathways are dysregulated in cancer. Dysregulation of the regulatory network results in less control of transcript levels in the cell. Hence, dysregulation is reflected in the heterogeneity of the transcriptome: the more dysregulated the pathway, the more the transcriptomic heterogeneity. We identify four scenarios for a transcriptomic heterogeneity increase (i.e., pathway dysregulation) in cancer: (1) activation of a molecular switch, (2) a structural change in a regulator, (3) a temporal change in a regulator, and (4) weakening of gene–gene interactions. These mechanisms are statistically motivated, explored in silico, and their plausibility to occur in vivo illustrated by means of oncogenomics data of breast cancer studies.
U2 - 10.1007/s11538-015-0103-7
DO - 10.1007/s11538-015-0103-7
M3 - Article
VL - 77
SP - 1768
EP - 1786
JO - Bulletin of Mathematical Biology
JF - Bulletin of Mathematical Biology
SN - 0092-8240
IS - 9
ER -