Abstract

Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited disorder characterized by the development of hundreds of colorectal polyps. If untreated, there is a 100% probability of these adenomas developing into colorectal cancer, although a total colectomy can significantly improve the prognosis and is the common course of action to treat FAP patients. Two important precursor lesions that progress into colorectal cancer in FAP patients are tubular adenomas (TA) and traditional serrated adenomas (TSA). These adenomas each have distinct morphology: TSAs are characterized by serrations and eosinophilic cytoplasm, while TAs are characterized by the rounded or tubular nature of their neoplastic glands. Proto-oncogenes KRAS and BRAF both play a role in each of these adenomas’ progression to colorectal cancer and often exhibit hotspot mutations in these adenomas. However, research regarding the prevalence and importance of BRAF and KRAS hotspot mutations in these adenomas is limited, as different studies have reported significantly different rates of KRAS and BRAF mutations in TSAs and TAs. Thus, the mutational landscape of KRAS and BRAF in TSAs and TAs must be investigated further to determine the prevalence of these hotspot mutations. In this research, DNA from polyps of FAP patients with TSA and TA morphology was extracted, amplified, and sequenced in order to determine their mutational status as a means of evaluating the mutational landscape of KRAS and BRAF in these adenomas.