title: Transcriptomic Heterogeneity in Cancer as a Consequence of Dysregulation of the Gene-Gene Interaction Network.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, P. O. Box 7057, 1007 MB, Amsterdam, The Netherlands. w.vanwieringen@vumc.nl.|Department of Mathematics, VU University Amsterdam, De Boelelaan 1081a, 1081 HV, Amsterdam, The Netherlands. w.vanwieringen@vumc.nl.
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.affiliation: Department of Mathematics, Leiden University, P. O. Box 9512, 2300 RA, Leiden, The Netherlands.
authors.forename: Aad W
authors.initials: AW
authors.lastname: van der Vaart
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D003198:Computer Simulation; D004843:Epistasis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D055641:Mathematical Concepts; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D059467:Transcriptome
keywords: Entropy; Gaussian graphical model; Gene expression; Multivariate normality; Pathway