ECE2020 Audio ePoster Presentations Pituitary and Neuroendocrinology (217 abstracts)
Role of NGS in the diagnostic work-up of pituitary tumors and ‘incidental findings’
Giulia Del Sindaco 1,2 , Elisa Sala 1 , Giulia Carosi 1,3 , Arianna Cremaschi 1,2 , Roberta Mungari 1 , Andreea Liliana Serban 1,3 , Beatrice Mantovani 1,2 , Rita Indirli 1,2 , Emanuele Ferrante 1 , Luca Persani 2,4 , Maura Arosio 1,2 & Giovanna Mantovani 1,2
1Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 2University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 3Sapienza University of Rome, Department of Experimental Medicine, Rome, Italy; 4Auxologico San Luca, Endocrinology Unit and Metabolic Diseases, Milan, Italy
Background: Pituitary tumors are mostly sporadic, but in less than 5% of cases they can be associated to genetic syndromes, so harbouring germline mutations. Familial pituitary tumors are often more aggressive, so it’s important to detect them, for both a better early diagnosis and genetic counselling. Before the development of Next-Generation Sequencing (NGS), Sanger sequencing was the most widely used method of DNA sequencing. Therefore, DNA samples were analysed following a phenotype-drivenstrategy, using direct sequencing of the coding regions of one single candidate gene at a time. Since 2000, the introduction of NGS, a massively parallel sequencing of millions of fragments of DNA, improved the accuracy of genetic testing with an overall reduction in time and costs. Consequently, genetic testing is more and more integrating into the clinical practice. In addition, some rare phenotypes are common to different clinical conditions caused by different genetic mutations. In this case NGS is useful to identify genotype-phenotype associations not recognized with single genes sequencing method, the so-called ‘incidental findings’.
Materials and methods: We carried out genetic testing in 25 patients (mean age 46.9), between November 2014 and September 2019. All patients received a diagnosis of pituitary tumor and were suspected to have a genetic syndrome according to the indications given by the literature. 14 patients were investigated for MEN-1 and 11 patients for FIPA. Gene analysis was performed with targeted NGS panel testing for the following genes: AIP, CDKN1b, CDC73, MEN-1, RET, PRKAR1A.
Results: 2 patients had a mutation in AIP, thus confirming the suspected FIPA (2/11, 18%). 21 patients were negative for mutations in all the analysed genes. In one patient with suspected MEN-1, we unexpectedly found a heterozygosis mutation in exon 7 of PRKAR1A (well known as responsible for Carney Complex). The last patient, with a suspected MEN-1 too, had a heterozygosis mutation in the exon-intron junction of exon 2 of CDKN1b (responsible for MEN-4).
Conclusions: Our experience shows that the use of NGS should be now considered as an important step in the diagnostic work-up of pituitary tumors with suspected germline mutations. Moreover, massively parallel sequencing may lead to ‘incidental findings’, with clear implications not only inclinical practice but also for its consequent ethical issues.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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