Publicaciones científicas
Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients
Maria Currás-Freixes 1 , Lucía Inglada-Pérez 2 , Veronika Mancikova 1 , Cristina Montero-Conde 1 , Rocío Letón 1 , Iñaki Comino-Méndez 1 , María Apellániz-Ruiz 1 , Lara Sánchez-Barroso 1 , Miguel Aguirre Sánchez-Covisa 3 , Victoria Alcázar 4 , Javier Aller 5 , Cristina Álvarez-Escolá 6 , Víctor M Andía-Melero 7 , Sharona Azriel-Mira 8 , María Calatayud-Gutiérrez 9 , José Ángel Díaz 10 , Alberto Díez-Hernández 11 , Cristina Lamas-Oliveira 12 , Mónica Marazuela 13 , Xavier Matias-Guiu 14 , Amparo Meoro-Avilés 15 , Ana Patiño-García 16 , Susana Pedrinaci 17 , Garcilaso Riesco-Eizaguirre 18 , Constantino Sábado-Álvarez 19 , Raquel Sáez-Villaverde 20 , Amaya Sainz de Los Terreros 21 , Óscar Sanz Guadarrama 22 , Julia Sastre-Marcos 23 , Bartolomé Scolá-Yurrita 24 , Ángel Segura-Huerta 25 , Maria de la Soledad Serrano-Corredor 26 , María Rosa Villar-Vicente 27 , Cristina Rodríguez-Antona 2 , Esther Korpershoek 28 , Alberto Cascón 2 , Mercedes Robledo 2
Background: Nowadays, 65-80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic-PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source.
Methods: The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL, the SDH genes, TMEM127, MAX and FH. 99 tumours from patients negative for germline screening were available and tested for RET, VHL, HRAS, EPAS1, MAX and SDHB.
Results: Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62×10(-10)). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0×10(-4) and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS.
Conclusions: We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening.
CITA DEL ARTÍCULO J Med Genet. 2015 Oct;52(10):647-56. doi: 10.1136/jmedgenet-2015-103218. Epub 2015 Aug 12