ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 S9.2 | DOI: 10.1530/endoabs.63.S9.2

The dos and don'ts of genetic testing in phaeochromocytoma

Mercedes Robledo


Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours with marked genetic heterogeneity, being the most inherited human tumour described so far. Around 40% of patients will be a carrier of a germline mutation in any of the know PPGL genes, and thus, for years most of studies have been performed on germline DNA. Findings from genetic testing in tumour DNA has dramatically changed the scenario. Nowadays, it is as relevant to make the screening on the germline DNA as to discard somatic mutations in those negative patients for the former analysis. From a daily basis genetic testing lab, there are important implications of having a genetic diagnosis in every single PPGL patient regardless the age of diagnosis or metastatic status, especially when the results would influence the management of the patient, or relatives at risk of being a mutation carrier. Where Next Generation Sequencing platforms are available, it is not only determinant the source of DNA sample to study, but also the availability of clinical information that will be used in the variant’s interpretation step. This is a challenging task not only for laboratories that very often must apply a plethora of functional assays to demonstrate pathogenicity, but also for professionals responsible of genetic counseling and patient management. Another factor that should not be overlooked is the importance of selecting appropriately the tumour material to work with. This critical step should be done by pathologists in order to avoid masked mutations and therefore, false negative results. An increase in the knowledge of the molecular mechanisms involved in PPGL initiation, progression, and metastasis is fundamental for optimizing clinical management of this complex disease. It make sense that genetic information could be useful for selecting therapeutic options, as in the most of PPGLs it is detected a germline or somatic mutation in a gene or molecular pathway that can be therapeutically targeted by at least one antitumor agent clinically available for another disease.

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