Oncogenes (and tumour suppressors) in endocrine tumours – current diagnostics and future approaches

Abstract

The rapid discovery of genetic changes associated with neoplasia has been successfully translated to clinical practice for several inherited endocrine tumour syndromes. These gene tests have current applications in diagnosis, presymptomatic detection, prognosis, and tumour subclassification, and are likely to allow for targeted therapies (pharmacogenomics) in the near future. Gene tests are available for the familial syndromes: multiple endocrine neoplasia type 1 ( MENIN ), type 2 ( RET ), hyperparathyroidism-jaw tumour syndrome ( HRPT2 ), neurofibromatosis type 1 ( NF1 ), von Hippel Lindau disease ( VHL ) and the phaeochromocytoma/paraganglioma syndromes caused by mutations in the genes encoding the succinate dehydrogenase subunits B, C and D ( SDHB , SDHC , SDHD , respectively). Arguably, targeted gene testing should be offered for all cases of medullary thyroid cancer, all parathyroid cancers and all phaeochromocytomas. A positive gene test establishes a molecular diagnosis and permits screening and early treatment for affected family members. For several of these gene tests, a positive result identifies additional risk for multi-organ disease requiring ongoing clinical surveillance. In addition to the above germline DNA tests, testing somatic (tumour) DNA may be clinically valuable in several scenarios such as for BRAF mutations in papillary thyroid cancers. The future for molecular diagnostics will include high-throughput mutation detection combined with improved genotype-phenotype correlations.