Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT Number: NCT06523582
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Neuroendocrine Neoplasm|Neuroendocrine Neoplasm of Gastrointestinal Tract|Neuroendocrine Neoplasm of Lung|Thymic Neuroendocrine Neoplasm|Neuroendocrine Tumor of Pancreas|Gastrointestinal Stromal Tumors|Medullary Thyroid Cancer|Paraganglioma|Pheochromocytoma|Primary Hyperparathyroidism|Pituitary Tumor|Multiple Endocrine Neoplasia Type 1|Multiple Endocrine Neoplasia Type 2|Multiple Endocrine Neoplasia Type 4|Carney Complex|Carney Stratakis Dyad|Carney Triad|Cowden Syndrome|DICER1 Syndrome|Li-Fraumeni Syndrome|Lynch Syndrome|Von Hippel-Lindau Disease|Familial Isolated Pituitary Adenoma|X-Linked Acrogigantism|Neurofibromatosis 1|Tuberous Sclerosis
Sponsor: Universidad Nacional Autonoma de Mexico
Collaborators: Instituto Mexicano del Seguro Social|Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 750
Study Design: Observational Model: |Time Perspective: p
Start Date: 2022-08-03
Completion Date: 2037-03-01
Locations: Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Cdmx, 06720, Mexico|Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Cdmx, 14080, Mexico|Red de Apoyo a la Investigación, Coordinación de la Investigación Científica, Universidad Nacional Autónoma de México, Mexico City, Cdmx, 14080, Mexico

Summary:
Neuroendocrine neoplasms (NENs) are a heterogeneous group of lesions derived from cells with the ability to produce hormones that may arise from multiple different organs. Their clinical behavior is quite variable, encompassing both benign lesions and aggressive tumors that invade surrounding and/or distant structures. NENs may also cause serious morbidity due to hormone oversecretion. NENs are among the most frequently inherited human tumors, presenting either isolated or as part of syndromes in which a single patient or family develops multiple tumors. There are also non-inherited changes in the genetic information of the tumor cells that are potential targets for treatment. Both inherited and non-inherited DNA defects can be identified using modern routine genetic tests which, unfortunately, are not widely available in Mexico.

This project seeks to uncover the genetic defects causing NENs in a large cohort of Mexican patients, using three different methods for genetic testing. Adult individuals with various types of NENs from two reference hospitals in Mexico City will be invited to participate. After completing informed consent, blood and, if possible, tissue samples will be obtained from all participants. Clinical details, laboratory results, imaging studies, and histopathological data at disease presentation will be retrieved.

An initial screening will be performed by analyzing changes in the sequence of multiple genes that have been associated with the occurrence of NENs. In cases with negative screening, a specific method to assess changes in the number of copies of the same genes will also be employed. Finally, sequences of all DNA regions encoding information required to make proteins will be obtained in selected cases. Analyses will be carried out in blood and, if available, also in tumor tissue samples from study participants. Screening of additional family members will be offered.

This project will accurately describe the repertoire of specific defects causing NENs in the study population, and will likely uncover and characterize novel genetic associations. The results will contribute for a better understanding of the alterations within and outside known driver genes that shape syndromic presentations, tumor behaviors, and inheritance patterns in individuals with NENs. These data will contribute to improve the information on the molecular bases of NENs, including alterations that can be used as therapeutic targets.

Primary Outcome Measures: Detection of a germline or somatic genetic defect of interest., Detection of a genetic defect classified as pathogenic, likely pathogenic, or of uncertain significance in accordance with the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology., Up to fifteen years from the date of recruitment.