In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Bioinformatics
in the School of Biological Sciences
Khalid A. Alhumimidi
Defends his thesis:
GENOMIC ANALYSIS OF COLORECTAL CANCER COMPLEXITY IN COMPARISON OF AFRICAN AMERICAN TO NIGERIAN PATIENTS
Tuesday, December 14, 2021
3:00 pm Eastern Time
https://bluejeans.com/804405036/4719
Thesis Advisor:
Dr. Gregory Gibson, Advisor
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Dr. I. King Jordan
School of Biological Sciences
Georgia Institute of Technology
Dr. John McDonald
School of Biological Sciences
Georgia Institute of Technology
Dr. Joseph Lachance
School of Biological Sciences
Georgia Institute of Technology
Dr. Olatunji Alese
Department of Pediatrics and Human Genetics
Emory University
Summary:
Colorectal cancer (CRC) is the third ranking diagnosed cancer in the US and worldwide. It is estimated to affect 1 in 25 individuals in the US throughout their lifetime. Mortality and morbidity rates due to CRC have been observed to vary among countries as well as between groups within the same country. The causes of CRC disparities are likely to include genetic and non-genetic factors (such as diet) and the combination of both. The US is among the countries with the highest CRC rates in the world and African Americans are reportedly the highest group within the US. In this thesis I contrast genomic and transcriptomic profiles of CRC tumor and matched healthy colon tissue biopsies of US African American (n=29) and Nigerian (n=10) patients. Recurrent somatic copy number variation (SCNV) was documented, and includes aneuploidy involving gains on chromosomes 13 and 20, and losses on chromosomes 4 and 18. Gene expression levels were correspondingly increased and decreased throughout the affected chromosome arms. To evaluate the tumor complexity and proliferation rate in the samples, replication-dependent histone genes expression was quantified and compared with expression of the cell proliferation antigen marker KI-67 gene (MKI67). A significant increase in the expression of the replication-dependent histone genes as well as MKI67 was observed in the African American samples compared to the Nigerian samples, implying a higher proliferation rate and complexity in African American. Since African American ancestry is largely derived from West Africa, these results implicate non-genetic factors as a major influence on the CRC disparity.
