PTEN Hamartoma Tumor Syndrome (PHTS) Collection

This iPSC collection serves as a model for PTEN hamartoma tumor syndrome (PHTS), a rare, autosomal dominant genetic condition caused by mutations in the PTEN gene. PHTS is characterized by benign, tumor-like growths (hamartomas) that can occur throughout the body.

Affected individuals have an increased lifetime risk of several cancers (particularly breast, thyroid, and endometrial cancer) and may also experience a range of additional clinical features, including macrocephaly, neurobehavioral, and neurocognitive deficits, including autism spectrum disorder, vascular anomalies, and gastrointestinal polyposis. Recent large-scale genomic studies suggest that pathogenic PTEN variants occur in approximately 1 in 9,000 to 1 in 13,000 individuals, indicating that PHTS is more prevalent than previously recognized. Currently, there are no health authority-approved therapies specific to PHTS.

The PTEN gene encodes a ubiquitously expressed tumor suppressor that negatively regulates the PI3K/AKT/mTOR signalling pathway, thereby affecting several cellular processes such as growth, survival, metabolism and migration.

The cell lines in this collection were deposited by Professor Mustafa Sahin and Dr. Elizabeth Buttermore at the Human Neuron Core in the Rosamund Stone Zander and Hansjoerg Wyss Translational Neuroscience Center at Boston Children’s Hospital in Boston, Massachusetts, with funding from PTEN Research.

The collection consists of iPSCs reprogrammed from fibroblasts or peripheral mononuclear cells from IRB-consented donors carrying the heterozygous PTEN variant, generated using Sendai virus methods. It also includes isogenic pairs and genomic allelic series established using CRISPR/Cas gene editing to either correct a patient-specific variant to establish lines with homozygous wild-type expression or introduce the variant to the healthy allele of the patient line to establish lines with homozygous variant expression.

Additional data on the hiPSC lines can be found under their corresponding hPSCreg ID numbers here.