Chandlee, Joel

Advisor Department

Cell and Molecular Biology




Genetic Testing; Lynch Syndrome; Cancer; Genetics; MLH1; Inherited Cancer


In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other tissue. Because the individual is being tested for a disease that is an inherited trait, the germline mutation will be present in every cell of the patient’s body. Geneticists search for specific markers within the human genome that are indicators of an inherited cancer syndrome. These markers can be changes in chromosomes, DNA, or proteins, depending on the suspected disorder. Common genes that are associated with hereditary cancers are BRCA1, MLH1, TP53, CDK4, and PTEN among others. Each oncogene presents with a phenotype that alters a biochemical process within the body that is essential for healthy cell development. Early diagnosis of an inherited cancer syndrome is vital in promoting a healthy course of treatment in the patient as well as helping researchers gain a greater understanding of the pathogenesis of relevant oncogenes.

This research paper was designed to investigate the methods used in genetic testing as well as demonstrate the importance of implementing genetic tests to individuals who appear to be at risk for cancer. To supplement this research, a real world case study, provided by Dr. Joseph Montanaro Jr. and Myriad Genetics, was evaluated. Specifically an individual who underwent the Myriad myRisk® genetic test and presented with a mutation known as Lynch Syndrome was studied. This particular inherited disorder leaves patients at extremely high risk for hereditary non-polyposis colon cancer (HNPCC) as well as several other forms of cancer. Lynch Syndrome is classified by mutations in DNA mismatch repair genes that provide instructions for repairing damaged DNA before cell division. The patient in this case study was heterozygous for the 113del (p.Thr45Glnfs*5) mutation that is expected to result in premature truncation of the MLH1 protein at amino acid position 49. This project attempts to understand why this is a particularly harmful mutation and to identify its role in the pathogenesis of Lynch Syndrome.