Abstract:
Introduction. According to the WHO, it is estimated that the annual number of cancer's cases
will increase by about 70% in the next two years.
Aim of the study. To evaluate and systematize pathogenetic factors that contribute to
cancerogenesis. Cancerogenesis is defined as the static process by which a normal cell acquires
properties that allow the development of malignant phenotype (uncontrolled proliferation, local
invasion and metastasis), or a cascade of events that lead to the transformation of a normal cell,
often a clonogenic cell (stem cell) into cancer. Cancerogenesis is the multistage process in which
mutations lead to the development of malignant phenotype, which is the result of multiple
interactions between various exogenous and endogenous factors. Cancerogenesis proceeds
through the accumulation of genetic and epigenetic changes that allow cells to break free from
the tight network of controls that regulate the homeostatic balance between cell proliferation and
cell death.
Conclusions. 1. In recent years, the development of genome-wide analytic methods has opened
the possibility of identifying simultaneously multiple changes in gene expression as well as in
genetic or epigenetic alterations affecting the genome of cancer cells. 2. The Mutator Phenotype
can be caused by a number of mechanisms, such as defects in cell-cycle regulation, apoptosis,
specific DNA repair pathways, or error-prone DNA polymerase, and it can have its source in
inherited genetic defects that make subjects prone to specific cancers. 3. Mutations in cancer
cells cover a wide range of structural alterations in DNA, including changes in chromosomes
copy numbers or chromosomal alterations encompassing millions of base-pairs such as
translocations, deletions or amplifications, as well as smaller changes in nucleotide sequences
such as point mutations affecting a single nucleotide at a critical position of a cancer-related gene
(Sugimura et al., 1992). These different kinds of alterations often co-exist within a single tumour.
4. TP53 mutations in plasma DNA have been reported in patients with cancers of the colon,
pancreas, lung, and liver. 5. EGFR and HER2 are often altered in diverse human cancers, by
amplification, point mutation, or both. Amplifications of EGFR have been detected in brain
cancers and in a small proportion of a number of epithelial cancers such as squamous oral or
esophageal cancer. Amplification and overexpression of HER2 are a frequent event in breast and
ovarian cancer (Harari and Yarden, 2000).
