Research News

Charis Eng, MD, PhD, was awarded a two-year, nearly $680 thousand grant from the PTEN Research Foundation to investigate if and how alterations in the genome influence clinical outcomes in individuals with PTEN hamartoma tumor syndrome (PHTS).

PHTS refers to a spectrum of rare genetic disorders defined by germline (heritable) mutations in the tumor suppressor gene PTEN. Individuals with PHTS face increased risk for certain cancers, cognitive and behavioral deficits, benign growths and tumors (hamartomas), and macrocephaly. However, clinical manifestations of PHTS vary greatly among patients and often are difficult to predict.

For example, subsets of well-defined disorders on the PHTS spectrum have been found to be characterized by either a high risk of certain cancers and/or autism spectrum disorder (ASD). Furthermore, some individuals with PHTS will experience debilitating overgrowths in their blood vessels or gut, but they will not develop cancer or ASD.

Preliminary data from Dr. Eng’s team indicate that disease outcomes in individuals with PHTS may be affected by other changes in the genome (an individual’s complete set of DNA, including protein-coding and noncoding elements) besides PTEN mutations. Comprehensive characterization of all potential genomic markers remains unrealized, however, because the majority of research has focused on the protein-coding regions, which make up only about one percent of the genome.

With this grant, Dr. Eng’s team will sequence the whole genomes of a large number of PHTS patients from around the world to understand if and how the remaining 99 percent of the genome (that is non-coding), known as “dark matter,” influences clinical manifestations of PHTS at the individual level.

“We are on a grand mission to identify targets for prevention and early treatment for PHTS,” Dr. Eng said. “Knowledge is power, and knowledge of factors that determine ‘who will get what’ is important to guide proactive preventative actions rather than reactive treatment of full-blown disease.”

Findings from this project will be shared through scientific meetings, and final data will be formally published with open access to allow maximum information dissemination.

Dr. Eng is the inaugural chair of the Genomic Medicine Institute and inaugural director of the Center for Personalized Genetic Healthcare, which includes the PTEN Multidisciplinary Clinic for children and adults with a confirmed or possible diagnosis within the PHTS spectrum. She was the first to link PTEN to Cowden syndrome, which is a PHTS disorder, and subsequently to ASD. In fact, PTEN alterations are one of the most common causes of ASD.