Endocrine Abstracts

Patient- and family center edendocrine cancer care encourages active collaboration between the departments of endocrinology, oncology, surgery, pathology, chemistry, radiology, nuclear medicine and clinical genetics. The implementation of high-throughput DNA/RNA sequencing platforms has allowed novel molecular information to be used to optimize primary endocrine cancer care including tumor classification, prognostic forecasting, stratification for targeted treatment in recurrent disease and the identification of patients at high risk for tumor development. Multiple Endocrine Neoplasia (MEN) type 1–2 and von Hippel-Lindau syndrome were among the first hereditary tumor predisposition syndromes to be recognized and over time the number of endocrine tumor syndromes and associated genes has expanded significantly. Depending on the specific endocrine tumor type, 10–30% of cases are associated with genetic factors, in which up to 15 different genes per tumor type may be implicated. The proportion of inherited disease in the context of the totaldisease population in clinical practice might be an underestimate owing to still unidentified genetic causes orbecause heredity is not recognized due to an unavailable, incomplete or misdiagnosed family history and/or variable penetrance. Identification of a causative germline mutation may not onlyhave important clinical implications for the index patient (proband), it also facilitates cascadetesting and surveillance of relatives in order to prevent, or at least allow early identification of, (pre)malignant conditions. Current challenges in known tumor predisposition syndromes include accurate estimates of variant pathogenicity, disease penetrance, genotype-phenotype relationships and the variable phenotypes within families, and from there to tailored treatment and surveillance guidelines. While endocrine neoplasia syndromes show many features commonly seen in familialdisease (early onset, family history, multifocal neoplasia, multiorgan involvement), some of these syndromes are considered to be phenotypically complex and heterogeneous. The use of whole exome sequencing for diagnostic and research purposes may lead to identification of a syndrome that was not in the initial differential diagnosis. The drawback of testing many genes is the complex interpretation of the results. Pre-test genetic counseling to establish the preferred sequence modality and tiered informed consent is therefore of utmost importance. Improving endocrine cancer genetics requires not only local, national and international collaborations between the medical disciplines involved but also the interaction between basic and clinical research, taking research from bench to beside and back again.