Title of project

Clinical and genetic characterization of Hereditary Endocrine Tumour Syndromes (the HETS-study)

Abstract

Hereditary endocrine tumour syndromes (HETS) are rare genetic conditions that increase the risk of developing tumours in hormone-producing glands, e.g. pheochromocytomas and paragangliomas (PPGLs). These tumours may be benign or malignant and often remain undiagnosed until symptoms appear, posing a significant risk to patient health. Despite their severity, clinical knowledge about how these diseases develop and how to best monitor at-risk individuals remains limited. This PhD project aims to improve risk stratification, diagnosis, and surveillance strategies for individuals with HETS, using an interdisciplinary approach that combines clinical genetics, endocrinology, epidemiology, and molecular biology. Three work packages will address:
(1) the creation of a national database of individuals with HETS, enabling comprehensive clinical and genetic characterisation;
(2) optimisation of surveillance strategies for both adults and children with disease-causing variants in SDHx genes, in collaboration with Dutch and Swiss clinical partners; and (3) the identification of possible DNA methylation patterns (episignatures) that may help distinguish disease-causing from benign genetic variants and potentially be utilized as new biomarkers and biological treatment targets.

Through large-scale data integration and international collaboration, this project will contribute to more personalised, effective, and resource-conscious care. The findings will be used to refine clinical guidelines and support future research into precision medicine for individuals at risk of rare hereditary endocrine cancers.