Tumor Gastric Clinical Trial
Official title:
Telomeric Abnormalities in Benign and Malignant Colorectal Diseases by Fluorescent in Situ Hybridization Technique
Colorectal carcinoma is a heterogeneous disease that is caused by the interaction of genetic
and environmental factors. colorectal carcinoma encompasses a complex disease with different
molecular pathways and biological characteristics arising from a multi-step process that
implicates several genetic and epigenetic events . The multi-step genetic model involves the
loss of function of tumor suppressor genes, such as adenomatous polyposis coli (APC),
Telomeres could be a promising marker due to the fact that their lengths change in the
colorectal polyp-carcinoma sequence . Moreover, telomere length (TL) is altered in blood
cells in patients with colorectal carcinoma
- These findings could suggest that changes in TL may take place before the development of
the tumor .
The two main forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's
disease (CD) are characterized by chronic intestinal inflammation and risk of progression to
colon cancer. One proposed cause of the latter characteristic is chromosome instability,
since the rearrangement of genetic material can lead to activation of oncogenes, loss of
tumor suppressor genes and other changes that lead to uncontrolled cell growth. Chromosome
instability is particularly associated with UC and has been observed in colon epithelial
cells and peripheral blood mononuclear cell. Since genomic instability in peripheral blood
mononuclear cells (PBMCs) has been used as a biomarker for global cancer risk in a number of
diseases, the latter observation suggests the possibility of a chromosome instability
syndrome in UC that could affect all tissues. One possible cause of chromosome instability is
telomere dysfunction .
Human chromosomes are capped and stabilized by telomeres, which not only protect them from
damage but also have a role in regulating cellular senescence. After reaching a critical
length, telomeres experience a double DNA change and cells will eventually enter senescence
(replication) or cell death . Telomere length and telomere shortening have been long
hypothesized to be a biological marker of aging at the cellular level and a potential
mechanism of carcinogenesis. Genomic instability is a critical factor in the initiation and
progression of human cancers. One mechanism that underlies genomic instability is loss of
telomere function .
fluorescent in situ hybridization is a molecular diagnostic technique that utilizes labeled
DNA probes to detect or confirm gene or chromosome abnormalities. fluorescent in situ
hybridization is often utilized for both research and diagnosis of hematological malignancies
and solid tumors. Conceptually, fluorescent in situ hybridization is a very straightforward
technique whereby a DNA probe is hybridized to its complementary sequence on chromosomal
preparations previously fixed on microscope slides . fluorescent in situ hybridization is
able to detect cells that have chromosomal abnormalities consistent with neoplasia .
There has been a surge of published studies which assessed the association between telomere
length and development of colorectal carcinoma. Thus, a meta-analysis addressing colorectal
carcinoma and telomere length would be a useful addition to the current information in this
area.
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