Research News

Charis Eng, MD, PhD, Dennis Lal, PhD, and Harry (Adrian) Lesmana, MD, were recently named recipients of VelaSano research awards. VeloSano is Cleveland Clinic’s flagship cancer research fundraising initiative, which has raised more than $24 million since its inaugural year in 2014. Drs. Eng, Lal and Lesmana will receive $125,000 over two years for their projects.

Predicting cancer risk in PTEN hamartoma tumor syndrome patients

Dr. Eng’s project will examine a potential biomarker of cancer risk in patients with PTEN hamartoma tumor syndrome (PHTS). PHTS is defined by germline mutations in the PTEN gene and significantly elevates the lifetime risk of certain cancers. However, cancer occurs in only some PHTS patients, and there are no methods to differentiate between who will develop cancer and who will not. With this project, Dr. Eng’s team will investigate if cell-free DNA (a specific form of DNA in the blood) can serve as a reliable predictor of individual cancer risk in PHTS patients. If successful, these observations may be applicable to all gene-associated cancers, including sporadic ones.

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 (designated as a PHTS Clinical Center of Excellence by the PTEN Hamartoma Tumor Syndrome Foundation) 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.

Understanding the genetics of low-grade neuroepithelial tumors

Dr. Lal’s project seeks to provide novel biological insights into the cause and genetic risk of low-grade neuroepithelial tumors (LGNTs), a group of pediatric brain tumors associated with chronic drug-resistant epilepsy. Specifically, using several genomic datasets, Dr. Lal’s team will search for novel LGNT-associated genes, explore if individuals with LGNTs have more cancer risk variants and identify LGNT subtypes based on mutational signatures (characteristic combinations of mutations).

Dr. Lal is assistant staff in the Genomic Medicine Institute.

Identifying novel genes in childhood cancer predisposition syndromes

Dr. Lesmana’s project will establish a clinical registry of data from individuals with familial cancer and a repository to store their biological materials. These data (which will be systematically collected and validated) and samples will then be analyzed to identify novel genes that predispose individuals to pediatric-onset cancer predisposition syndromes and pinpoint novel genes and/or genetic variants that influence clinical presentation (disease severity) in individuals with known cancer predisposition syndromes.

Dr. Lesmana is a pediatric oncologist in Cleveland Clinic Children’s and a medical geneticist in the Center for Personalized Genetic Healthcare. He also conducts research on the role of JAK3 mutations in the pathogenesis of lymphoproliferative disorders in the lab of Bin Zhang, PhD.

Image (left to right): Charis Eng, MD, PhD; Dennis Lal, PhD; Harry (Adrian) Lesmana, MD