Epigenetic Modifications in Tumor Suppressor Genes (TSG) 17In this chapter, we analyze the current evidence on the role of epigenetic
mechanisms involved in the progression of various types of cancer and their
clinical relevance.
EPIGENETIC ALTERATIONS IN DIFFERENT TYPES
OF CANCER ASSOCIATED TO TSG
The BRCA1 (breast cancer 1) gene is a tumor suppressor gene that
encodes a protein involved in the cell cycle regulation and DNA damage
repair. Its action prevents the cell uncontrolled proliferation. Several evidence
show, that different mutations of this gene are involved in some types of
cancer, especially breast cancer. Also, it has been observed that
hypermethylation at the BRCA1 gene promoter inhibits the transcription and
promotes the genesis of cancer 6 . Evidence of hypermethylation in other
TGS associated with breast cancer has been found. In this sense, it has been
observed the silencing of RASSF1A (Ras association domain family 1A),
SLIT2 (Slit Guidance Ligand 2) and WIF1 (WNT Inhibitory Factor 1) by
promoter hypermethylation in hereditary breast cancer 7 . The silencing of
the RASSF1A by promoter methylation is also involved in kidney
tumorigenesis 8 . In accordance with these evidences, Papadopoulou et.al 9 ,
showed the RASSF1A promoter hypermethylation in plasma samples obtained
from patiens with breast cancer. This study shows that free-circulating DNA
can be detected in cancer patients and suggests a noninvasive approach for
early detection of cancer.
The loss of expression of RASSF through promoter methylation is
associated with many types of cancers such as leukemia, melanoma, breast,
prostate, neck, lung, brain, colorectal and kidney cancers 5 .
The inactivation of TP53 and retinoblastoma TSG by promoter
methylation has been demonstrated in Squamous Cell Carcinomas (SCC), the
most aggressive type of skin cancer 10 .
PRDM (PRDI-BF1 and RIZ) family proteins are factors of transcription
that act as suppressors of tumors in humans and have an important role in cell
differentiation and malignant transformation. It has been shown the
inactivation of PRDM by promoter hypermethylation in squamous cell
carcinoma of lung and adenocarcinomas 11 . Also, it has been demonstrated
the involvement of PRDM11 in B-cell lymphomagenesis. Fog et. al. 12
showed in animal models that PRDM11 inactivation by hypermethylation