The Transition from Cancer “omics” to “epi-omics” through Next- and Third-Generation Sequencing

Abstract

Deciphering cancer etiopathogenesis has proven to be an especially challenging task since the mechanisms that drive tumor development and progression are far from simple. An astonishing amount of research has revealed a wide spectrum of defects, including genomic abnormalities, epigenomic alterations, disturbance of gene transcription, as well as post-translational protein modifications, which cooperatively promote carcinogenesis. These findings suggest that the adoption of a multidimensional approach can provide a much more precise and comprehensive picture of the tumor landscape, hence serving as a powerful tool in cancer research and precision oncology. The introduction of next- and third-generation sequencing technologies paved the way for the decoding of genetic information and the elucidation of cancer-related cellular compounds and mechanisms. In the present review, we discuss the current and emerging applications of both generations of sequencing technologies, also referred to as massive parallel sequencing (MPS), in the fields of cancer genomics, transcriptomics and proteomics, as well as in the progressing realms of epi-omics. Finally, we provide a brief insight into the expanding scope of sequencing applications in personalized cancer medicine and pharmacogenomics.

Omics-Based Investigations of Breast Cancer

“…In-depth investigations into the molecular bases of BC phenotypes, development, progression, and metastasis are required for accurate diagnoses, prognoses, and assessments of the response to therapies for improving long-term patient survival [ 2 ]. The term “omics” gathers various fields of study that explore patients’ bodies at different molecular levels, ranging from the genome and transcriptome to the proteome and metabolome [ 3 ]. Moreover, interactomics promotes a holistic view in BC research by constructing and characterizing the protein–protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping.…”

“…Moreover, interactomics promotes a holistic view in BC research by constructing and characterizing the protein–protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping. Recently, three “epi-omics” fields, epigenomics, epitranscriptomics, and epiproteomics, have emerged, in order to explore the modifications that occur on the DNA, RNA, and proteins, respectively, for an advanced understanding of the cellular structure and function [ 3 ]. Novel omics fields, such as epichaperomics and epimetabolomics, could investigate the modifications in the interactome induced by cellular stressors and provide proteome-wide changes in PPI [ 4 ] and metabolites removed from their classical function, known as epimetabolites [ 5 ], respectively, as drivers of BC-causing phenotypes.…”

Advantages and challenges associated with bisulfite-assisted nanopore direct RNA sequencing for modifications

“…The epitranscriptome is the collection of chemical modifications on RNA that are essential for the structure and stability of RNA, translation efficiency of mRNA, and recognition of self vs. non-self RNAs, and they are involved in nearly all other cellular functions of RNA. 1,2 The epitranscriptome is a dynamic system under intense study, in which the benefits of future discoveries include an improved understanding of gene regulation, new targets for therapeutic intervention of disease, and personalized medicine when we understand the RNA modification signatures of particular diseases. 1,2 Classically, modifications to RNA were found by harvesting cellular RNA and then completely digesting it with nucleases and phosphatase to its nucleoside components followed by TLC or LC-MS/MS analysis.…”

“…1,2 The epitranscriptome is a dynamic system under intense study, in which the benefits of future discoveries include an improved understanding of gene regulation, new targets for therapeutic intervention of disease, and personalized medicine when we understand the RNA modification signatures of particular diseases. 1,2 Classically, modifications to RNA were found by harvesting cellular RNA and then completely digesting it with nucleases and phosphatase to its nucleoside components followed by TLC or LC-MS/MS analysis. 3,4 These experiments have identified 4140 base and sugar modifications on RNA polymers from all phyla of life.…”