Resumen de Clinical and genetic characterization of 145 spanish patients diagnosed with PTEN hamartoma tumor syndrome
The PTEN hamartoma tumor syndrome (PHTS) is a rare disease characterized by a large phenotypic variability of benign lesions together with a high predisposition to develop several cancer types (breast, thyroid, endometrial, renal, colorectal and melanoma). This hereditary syndrome is associated to germline mutations in the PTEN gene, although a considerable proportion of patients are not explained by this gene. Altogether, this results in the lack of awareness on the PHTS, underdiagnosis and poor management of these patients.
The first general objective is to characterize the disease in Spanish patients, both at a genetic level and at a clinical level, together with the comparison of our results with that obtained in other studied populations and the evaluation of the usefulness of the diagnostic criteria. The second objective is to look for other genetic factors that can be involved in the phenotype of the PHTS patients who do not harbor PTEN mutations.
To accomplish these objectives, we have gathered a series of 145 Spanish patients diagnosed with PHTS with their respective clinical information and biological samples. The use of a specific checklist allowed us to review the clinical features of interest, and the use of conventional genetic techniques (Sanger, MLPA, aCGH), together with high-throughput procedures (NGS and WES) enabled the molecular characterization, focusing not only in PTEN but also searching for other genes. Moreover, the functional studies gave insights into the implications in pathogenicity of different variants of unknown significance in PTEN.
The results of this work were used to state several recommendations for the diagnosis: the application of the most useful clinical features to drive genetic testing and the performance of this through multigene panels to detect other possibly altered genes that might confer additional clinical risks. Regarding the follow-up, it is relevant to do obesity check-ups and to anticipate the cancer screenings. Moreover, several findings of this study set the basis for future research.
Overall, this work contributes to accelerate and improve the diagnosis and patient care of the PHTS patients.
