Genomics of PPGL Tumors

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors with one of the highest hereditary burdens in oncology, yet data from Saudi Arabia remain limited despite a large national caseload and frequent late, metastatic presentations. This project will perform comprehensive genomic profiling of approximately 450 PPGL patients using paired tumor–normal whole-exome sequencing, RNA-seq, and targeted next-generation sequencing panels. Leveraging the unique demographic context of high consanguinity and large multi-generation families, we aim to:

1. Define the genomic landscape of PPGLs in Saudi Arabia.

2. Delineate genotype–phenotype correlations including penetrance, age at onset, metastatic risk, therapy response, and outcomes.

3. Identify additional germline modifiers and somatic/epigenetic drivers that explain phenotypic heterogeneity within canonical driver-defined clusters.

4. Build predictive models that integrate molecular features with clinical, pathological, and imaging data to stratify risk and guide management.

The study draws on an institutional database of ~1,000 managed PPGL cases and established NGS/bioinformatics infrastructure, ensuring feasibility and statistical power. Anticipated impacts include discovery of novel susceptibility genes, Saudi-specific reference data for clinical interpretation, and validated biomarkers for aggressiveness and therapy response. The findings will directly inform tailored national guidelines for family screening, surveillance timing, and precision treatment selection—advancing earlier diagnosis, reducing morbidity from metastatic disease, and aligning with health system priorities under Vision 2030.