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
ISSN: 17501172
Editorial
BMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, GB
Tipo de documento: Article
Volumen: 17 Número: 1
Páginas:
WOS Id: 000762360000001
ID de PubMed: 35227301
imagen All Open Access, Gold

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