Considerations on diagnosis and surveillance measures of PTEN hamartoma tumor syndrome: clinical and genetic study in a series of Spanish patients
Por:
Pena-Couso L., Ercibengoa M., Mercadillo F., Gómez-Sánchez D., Inglada-Pérez L., Santos M., Lanillos J., Gutiérrez-Abad D., Hernández A., Carbonell P., Letón R., Robledo M., Rodríguez-Antona C., Perea J., Urioste M., Alonso M.Á., Andrés R., Arévalo S., del Mar Arias M., Balmaña J., Beristain E., Blanco I., Boronat M., Brunet J., Cózar M.V., del Campo M., Díaz A., Gabau E., Barcina M.J., González M., Guitart M., Hernán I., Hernández H.S., Hernando S., Lacambra C., Lasa A., Lastra E., Llort G., del Rosario Marín M., Marrupe D., Martínez F., Martínez V., Martorell L., Orera M., Pedrinaci S., Pérez P., Pineda M., Plasencia A.M., Cajal T.R., Robles L., Rodà D., Rodríguez N., Rosell J., Sáez R., Salvat M., Sánchez A., Santana A., Soto J.L., Toll A., Tuneu A., Vázquez C.
Publicada:
1 ene 2022
Resumen:
Background: The limited knowledge about the PTEN hamartoma tumor syndrome (PHTS) makes its diagnosis a challenging task. We aimed to define the clinical and genetic characteristics of this syndrome in the Spanish population and to identify new genes potentially associated with the disease. Results: We reviewed the clinical data collected through a specific questionnaire in a series of 145 Spanish patients with a phenotypic features compatible with PHTS and performed molecular characterization through several approaches including next generation sequencing and whole exome sequencing (WES). Macrocephaly, mucocutaneous lesions, gastrointestinal polyposis and obesity are prevalent phenotypic features in PHTS and help predict the presence of a PTEN germline variant in our population. We also find that PHTS patients are at risk to develop cancer in childhood or adolescence. Furthermore, we observe a high frequency of variants in exon 1 of PTEN, which are associated with renal cancer and overexpression of KLLN and PTEN. Moreover, WES revealed variants in genes like NEDD4 that merit further research. Conclusions: This study expands previously reported findings in other PHTS population studies and makes new contributions regarding clinical and molecular aspects of PHTS, which are useful for translation to the clinic and for new research lines. © 2022, The Author(s).
Filiaciones:
Pena-Couso L.:
Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Ercibengoa M.:
Respiratory Infection and Antimicrobial Resistance Group, Infectious Diseases Area, BioDonostia
Mercadillo F.:
Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Gómez-Sánchez D.:
Hereditary Cancer Laboratory, 12 de Octubre University Hospital, i+12 Research Institute, Madrid, Spain
Clinical and Translational Lung Cancer Research Unit, i+12 Research Institute and Biomedical Research Networking Center in Oncology (CIBERONC), Madrid, Spain
Inglada-Pérez L.:
Biostatistics Unit, Statistics and Operational Research Department, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
Santos M.:
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Lanillos J.:
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Gutiérrez-Abad D.:
Medical Oncology Service, University Hospital of Fuenlabrada, Fuenlabrada, Spain
Hernández A.:
Dermatology Service, University Hospital of Fuenlabrada, Fuenlabrada, Spain
Carbonell P.:
Biochemistry and Clinical Genetics Centre, Virgen Arrixaca University Hospital, Murcia, Spain
Letón R.:
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Robledo M.:
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Rare Diseases Networking Biomedical Research Centre (CIBERER), Madrid, Spain
Rodríguez-Antona C.:
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Rare Diseases Networking Biomedical Research Centre (CIBERER), Madrid, Spain
Perea J.:
Surgery Department, Fundación Jiménez Díaz University Hospital, Madrid, Spain
Health Research Institute-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Urioste M.:
Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Alonso M.Á.:
Virgen del Camino Hospital, Pamplona, Spain
Andrés R.:
Lozano Blesa Hospital, Zaragoza, Spain
Arévalo S.:
Hospital of Donostia, Donostia, Spain
del Mar Arias M.:
Virgen del Camino Hospital, Pamplona, Spain
Balmaña J.:
Vall d’Hebrón Hospital, Barcelona, Spain
Beristain E.:
Txagorritxu Hospital, Vitoria-Gasteiz, Spain
Blanco I.:
Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain
Boronat M.:
Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain
Brunet J.:
Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain
Cózar M.V.:
Virgen de Valme Hospital, Sevilla, Spain
del Campo M.:
Vall d’Hebrón Hospital, Barcelona, Spain
Díaz A.:
Móstoles Hospital, Móstoles, Spain
Gabau E.:
Parc Taulí Hospital, Sabadell, Spain
Barcina M.J.:
Basurto Hospital, Bilbao, Spain
González M.:
Can Misses Hospital, Ibiza, Spain
Guitart M.:
Parc Taulí Hospital, Sabadell, Spain
Hernán I.:
Terrassa Hospital, Terrassa, Spain
Hernández H.S.:
Sant Joan de Déu Hospital, Esplugues de Llobregat, Spain
Hernando S.:
Alcorcón Hospital, Alcorcón, Spain
Lacambra C.:
Severo Ochoa Hospital, Leganés, Spain
Lasa A.:
Sant Pau Hospital, Barcelona, Spain
Lastra E.:
Hospital of Burgos, Burgos, Spain
Llort G.:
Parc Taulí Hospital, Sabadell, Spain
del Rosario Marín M.:
Puerta del Mar Hospital, Cádiz, Spain
Marrupe D.:
Móstoles Hospital, Móstoles, Spain
Martínez F.:
Nuestra Señora de La Candelaria Hospital, Santa Cruz deTenerife, Spain
Martínez V.:
La Paz Hospital, Madrid, Spain
Martorell L.:
Sant Joan de Déu Hospital, Esplugues de Llobregat, Spain
Orera M.:
Gregorio Marañón Hospital, Madrid, Spain
Pedrinaci S.:
Virgen de Las Nieves Hospital, Granada, Spain
Pérez P.:
San Carlos Hospital, Madrid, Spain
Pineda M.:
Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain
Plasencia A.M.:
Asturias Central Hospital, Oviedo, Spain
Cajal T.R.:
Sant Pau Hospital, Barcelona, Spain
Robles L.:
12 de Octubre Hospital, Madrid, Spain
Rodà D.:
Parc Taulí Hospital, Sabadell, Spain
Rodríguez N.:
La Paz Hospital, Madrid, Spain
Rosell J.:
Son Dureta Hospital, Palma, Spain
Sáez R.:
Hospital of Donostia, Donostia, Spain
Salvat M.:
Sant Joan de Reus, Tarragona, Spain
Sánchez A.:
Puerta de Hierro Hospital, Madrid, Spain
Santana A.:
Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain
Soto J.L.:
General Hospital of Elche, Elche (Alicante), Spain
Toll A.:
Del Mar Hospital, Barcelona, Spain
Tuneu A.:
Hospital of Donostia, Donostia, Spain
Vázquez C.:
Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain
All Open Access, Gold
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