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Georgia Journal of Science

Article Title

EXPRESSION OF MITOCHONDRIAL GENOME ALTERATION AS A POTENTIAL BIOMARKER FOR COLORECTAL ADENOPOLYPS IN RELATIVE TO AGE AND RACE

Abstract

Colorectal cancer (CRC) is a major cause of morbidity and mortality in the United States. The precision of an appropriate staging of colorectal polyp progression to cancer is misperceived among pathologists as well as doctors. Alternative approaches, such as identification of molecular markers associated with CRC progression, will be a useful predictive tool, to decrease the incidence colorectal cancer. The mitochondrial DNA (mtDNA) is predominantly susceptible to mutations because of high levels of reactive oxygen species (ROS) within the organelle. The cumulative frequency of mitochondrial genome mutations is age-related. Given that colorectal cancer is most frequently seen in older people, mtDNA mutations may play a vital role in CRC tumorigenesis which may inhibit oxidative phosphorylation due to increase ROS production. This study aims to identify a profile of mtDNA mutations/protein expression patterns in the early stages of colorectal tumors within and among African-American (AA) and Caucasian patients relative to age stratification. A combination of PCR-based sequencing and qRT-PCR technologies were employed to determine the mtDNA variants and different proteins expression levels in 16 CRC tissues samples obtained from the University of Alabama-Cooperative Human Tissue Network. Fifty-eight mtDNA mutations were identified out of which 93% of mutations were somatic and 7% were germline mutation. Most germline mutations were found in COIII region. Three of the mutations of COIII Adel9409, A9437G Gdel9438 were not reported previously. Additionally, the relative RNA expression in ATP6 region in the early stages CRC adenoma was higher in AA compare to Caucasian tissue samples. Our preliminary results suggest that there are certain mitochondrial mutations/expressions that may be associated with specific adenoma stages. Subsequently, our findings may aid in designing new clinical strategies for early screening and prevention in individuals with high risk.

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