Integrating “Omics” Data for Quantitative and Systems Pharmacology in Translational Oncology - Bioanalysis Advanced Materials Methods and Devices - page 186

Conversely, chromosomal deletions represent the copy number reductions that may
result in the complete absence of a DNA sequence from the cancer genome.
Usually, amplifications occur at regions enriched with oncogenes and deletions
happen at regions enriched with tumor suppressor genes.
12.2.2 Epigenomics
CpG site methylation . Epigenetic modifications are defined as heritable information
other than nucleotide sequences. DNAmethylation and histone modifications are the
two major classes of epigenetic. Epigenetics are now known to regulate a wide range
of physiological and pathological processes, including cancer. DNA methylation is
one of the most important epigenetic alterations and plays a critical functional role in
development, differentiation, and disease [ 22 , 44 ]. Promoter regions are usually
enriched with CpG dinucleotides, known as CpG islands; and hypermethylation of
these islands correlates with transcriptional silencing of tumor suppressor genes
[ 36 ]. Conversely, increased expressions of oncogenes were associated with
hypomethylation [ 13 ]. This hypomethylation is known to contribute to cancer cell
phenotypes through loss of imprinting and genomic instability that characterizes
tumors [ 13 ]. Furthermore, tumorigenesis of several cancers was also marked by
specific methylation changes in their genomes [ 101 ]. Therefore, constructing a
global methylation profile can lead to the discovery of candidate genes that correlate
to therapeutic outcomes [ 70 , 80 ] and patient survival in cancer [ 64 ].
12.2.3 Transcriptomics
Gene expression . Each of the genetic and epigenetic changes described previously
in cancer genome can alter the expression levels of genes or noncoding RNAs
(including both microRNAs and long noncoding RNAs). Some of these
modifications can alter the splicing patterns of a gene to generate different variants
of transcripts in cancer. These changes ultimately translate into altered functions,
leading to the development of cancer.
12.2.4 Translational Bioinformatics for “Omics” Data
The development of powerful and scalable high-throughput methods to interrogate
cancer genome has transformed cancer research over the past decade. The applica-
tion of such technologies coupled with advanced bioinformatics in cancer research
has facilitated the discovery of new oncogenes and their associate in various cancers.
Many of the gene expression changes can be assessed by microarray analysis. In fact,