ECE2014 Poster Presentations Endocrine tumours and neoplasia (99 abstracts)
Our experience in the evaluation criteria used for the genetic study of patients suspected of being affected by multiple endocrine neoplasia type 1 and mutational spectrum
Josep Oriola 1 , Antoni Sitges 2 , Albert Goday 2 , S Martínez 3 , Carles Villabona 4 , Jose Manuel Gómez 4 , Lourdes Loidi 5 , Isabel Salinas 6 , Manel Puig-Domingo 6 , E González-Romero 7 , J A García-Arnés 8 , Albert Lecube 8 , Jordi Mesa 9 , Rafael Simó 9 , J Rosell 10 , F Sánchez-García 11 , Immaculada Recas l2 , Josefina Biarnés l2 , Eduarda Pizarro 13 & Irene Halperin 1
1Hospital Clinic, Barcelona, Spain; 2Hospital del Mar, Barcelona, Spain; 3Hospital General Universitario, Elda, Alicante, Spain; 4Hospital de Bellvitge, Hospitalet LL., Barcelona, Spain; 5Hospital Clínico Universitario, Santiago de Compostela, Spain; 6Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 7Hospital Provincial, Málaga, Spain; 8Hospital U. Arnau de Vilanova, Lleida, Spain; 9Hospital de la Vall d’Hebron, Barcelona, Spain; 10Hospital Son Espasses, Palma de Mallorca, Spain; 11Hospital Dr Negrín, Gran Canaria, Spain; 12Hospital Dr J Trueta, Girona, Spain; 13Hospital de Mataró, Mataró, Barcelona, Spain.
Introduction: The autosomal dominant multiple endocrine neoplasia type 1 (MEN1), characterized by parathyroid hyperplasia (PH), neuroendocrine digestive tumours (NET) and pituitary adenomas (PA), is due to mutations in the tumor suppressor gene MEN1 encoding a 610-amino acid protein, menin. Guidelines recommend MEN1 mutational analysis in index cases with two or more MEN1-associated tumours, in first-degree relatives of mutation carriers and when clinical data suggest MEN1. We performed MEN1 genetic analysis in patients referred by Spanish endocrinologists and geneticists from 1997 to 2013. Our aim is to compare our results with inclusion criteria from MEN1 guidelines in order to improve our insight on mutations and phenotype spectrum.
Material and methods: The coding region (exons 2–10), 5′UTR region and intron–exon boundaries of MEN1 gene were analyzed in 162 index-case patients. When no mutation was thus found, MLPA was performed.
Results: 115 (71%) females and 47 (29%) males were studied. Mutations were identified in 56 (35%), 35 females and 21 males; 32 (57%) had familial history of MEN1. 91% presented PH, 55% had NET and 46% had PA. We detected 52 different mutations: 20 frameshift (38%), 18 missense (35%), seven nonsense (14%), six splicing (11%) and one regulatory (2%) mutations; 22 (42%) have not been previously described. Mutations were found in 9/11 (82%) cases with three MEN1-related tumours, 14/38 (37%) with PH and PA, 19/27 (71%) with PH and NET, 0/2 (0%) with PA and NET, 9/59 (16%) with PH, 1/4 (25%) with PA and 4/22 (19%) with NET. 3/9 positive cases with isolated familial PH showed missense mutation.
Conclusions: Our data support current referral criteria for MEN1 molecular genetic testing. The probability of finding an MEN1 mutation is correlated with the number of MEN1-related tumours. Patients with PH and NET are more likely to carry a MEN1 mutation than those with PH and PA. Our data do not suggest that isolated familial PH is associated with missense mutations. MEN1 mutations were also found in cases with just one tumour, highlighting the importance of analyzing these cases, since a positive result has a decisive clinical impact in the patient and familial context.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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