Neuroendocrinology and Pituitary

SUN-073 - Exploring the Clinical Phenotypes Associated with Genetic Drivers of Neuroendocrine Neoplasia

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

DC

Dalia Cuenca, n/a

Departamento de Endocrinología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Distrito Federal, Mexico

Co-Author(s)

CR

Claudia Ramírez-Rentería, n/a

Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social
Mexico City, Distrito Federal, Mexico
SL

Susana M. López-Zelocualtecatl, n/a

Red de Apoyo a la Investigación, Coordinación de la Investigación Cientifica, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Distrito Federal, Mexico
JZ

Julia M. Zuarth-Vázquez, n/a

Internal Medicine Unit and Metabolism Clinic, Médica Sur Clinic and Foundation
Mexico City, Distrito Federal, Mexico
MR

Maribel Rodríguez-Torres, n/a

Departamento de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Distrito Federal, Mexico
EE

Etual Espinosa-Cárdenas, n/a

Departamento de Endocrinología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social
Mexico City, Distrito Federal, Mexico
MG

Manuel García-Sáenz, n/a

Departamento de Endocrinología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social
Mexico City, Distrito Federal, Mexico
MT

María T. Tusié-Luna, n/a

Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán/ Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México
Mexico City, Distrito Federal, Mexico
YS

Yayoi X. Segura-Kato, n/a

Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán/ Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México
Mexico City, Distrito Federal, Mexico
GB

Gabriela A. Buerba-Romero-Valdés, n/a

Departamento de Cirugía Endocrina, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Distrito Federal, Mexico
AG

Armando Gamboa-Domínguez, n/a

Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Distrito Federal, Mexico
AR

Alfredo Adolfo Reza Albarrán, n/a

Endocrinologist
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Distrito Federal, Mexico
NP

Nathan Pankratz, n/a

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School
Minneapolis, Minnesota, United States
JL

John Lane, n/a

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School
Minneapolis, Minnesota, United States
FF

Fabio R. Faucz, PhD

HCA Healthcare
Tampa, FL, United States
JM

James L. Mills, n/a

Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Bethesda, Maryland, United States

Senior Author/Primary Investigator(s)

LH

Laura C. Hernandez-Ramirez, MD, PhD

Associate Researcher C
National Autonomous University of Mexico
Mexico City, Mexico

Introduction. The extended use of genomic testing has uncovered both novel drivers and clinical presentations for neuroendocrine neoplasms (NENs) beyond the well-known classic familial isolated and syndromic phenotypes. Additional investigation on the spectrum of genetic entities linked to NENs is therefore warranted.
Aim. To determine the type, frequency, and associated clinical presentations of genetic drivers of multiple types of NENs in a large cohort.
Methods. We recruited 189 unrelated adults with NENs (73.5% females) from two reference centers in Mexico City (2022-2025). A custom next generation sequencing panel (pNGS) for 53 (n=90) or 54 (n=51) NEN-associated genes was used to screen 141 participants (seven with paired tumor genotyping). Mutational hotspots were analyzed in seven tumors and exome sequencing (ES) was completed in 32 cases with negative pNGS. Routine genetic testing (single-gene Sanger, n=37; diagnostic pNGS, n=11) was performed for the other probands (n=48). Targeted screening was performed in 62 additional members from 26 families.
Results. Thirty-four pathogenic or likely pathogenic variants (P/LPV, two somatic and 32 germline) were identified in one-quarter of probands (n=48); 91.2% were single nucleotide variants or indels (n=31) and 8.8% were copy number variants (n=3). MEN1 exhibited the most defects (n=13), followed by RET (n=8) and VHL, AIP, and SDHB (each n=3 variants). NF1, SDHA, SDHC, SDHD and USP8 showed single defects. Probands with P/LPV were younger at disease onset and at diagnosis than those without (27.7±11.9 vs 40[24.3-54] years, P=0.0001, and 29.2±11.9 vs 40.5[25-55.8] years, P=0.0003); 34.8% (n=16) were sporadic. Diagnostic yield was 100% in multiple endocrine neoplasia (MEN) 2B (n=3/3) and neurofibromatosis type 1 (NF1, n=1/1), 66.7% in Von Hippel Lindau syndrome (n=4/6), 58.3% in MEN2A (n=7/12), 45.7% in MEN1 (n=16/35), 33.3% in gigantism or young-onset acromegaly (n=4/12), 31.3% in medullary thyroid carcinoma (n=5/16), 16.7% in primary hyperparathyroidism (n=2/12), 14.8% in paragangliomas (PGLs, n=4/27), 5% in MEN-like (n=1/20), and 3.1% in other pituitary neuroendocrine tumors (PitNETs). Unconventional clinical associations were observed for NF1 (PitNET with NF1), SDHA (sporadic MEN1), and SDHB (typical aggressive PGLs in two individuals, but coexistent PGL and duodenal NET in another case). ES ruled out defects in cancer-related genes. Among family members, 41.9% (n=26) were variant carriers.
Conclusions. While some strong phenotype-genotype correlations exist, genetic drivers of NENs can lead to variable presentations. Aside from revealing rare phenotypes, the study of populations typically underrepresented in international studies, such as ours, can contribute to improving the precision of variant classification and, ultimately, uncover novel genetic drivers of neuroendocrine tumorigenesis.

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