Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis

Cancers are the consequence of combined genetic and epigenetic changes induced by environmental/dietary factors that trigger inappropriate activation or inactivation of specific genes leading to neoplastic transformation.

Most common mutations in TP53 (A) and EGFR (B). “Hotspot” mutations are colour-coded. The region encompassing residues 753–758 in EGFR is often targeted by small, in-frame deletions.

(A) DNA methylation, the covalent addition of a methyl group to the cytosine base in DNA, may be set up de novo (by DNA methyltransferase DNMT3A and DNMT3B) and maintained (by DNMT1) after DNA replication. (B) N-terminal “tails” of core histones are subject of different covalent modifications, the combinations of which are proposed to constitute the “histone code” that extends and modulates genetic (DNA) code.

Rational treatment design. Six major mechanisms that are systematically deregulated in cancer are depicted (boxes), as well as the molecular mechanism that are responsible for their alterations. Blue arrows indicate possible therapeutic approaches specifically targetting each of these mechanisms.