From the human genome to the epigenome of cancer: the use of high technology in molecular oncology

Abstract

Fifteen years after the publication of the full sequence of the human genome which revolutionized medicine and biotechnology, profound elucidation of the molecular mechanisms of genetic disorders remains a challenge. National and international institutions conduct a number of research projects in genomics. Some of them are focused on the characterization of functional elements of the genome (e.g., the Genome Browser database by the ENCODE consortium), some gather information on polymorphisms (HapMap, The 1000 Genomes Project) and mutations (The Human Gene Mutation Database), while other are specifically dedicated to the genomic characterization of cancer (The Cancer Genome Atlas, The Pediatric Cancer Genome Project). Even though the projects are conducted independently, juxtapositions of the constantly updated project data may be performed, leading to interesting results. The genome-wide association studies (GWAS) allowed the identification of millions of SNPs and short insertions/deletions, as well as thousands of structural variants of polymorphic gene products. Further data-mining studies allowed the distinction between synonymous and nonsynonymous SNPs, which became the basis for the epidemiological studies of various types of genetic disorders. The results of the sequencing of entire genomes and transcriptomes may be useful in the identification of novel prognostic and predictive markers. High-throughput technologies are emerging methods in molecular diagnostics, furthermore the correlation of DNA methylation patterns and gene expression profiles may also provide useful results in cancer diagnostics.