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Germline genetic variants in pheochromocytoma/paraganglioma: single-center experience. | LitMetric

Germline genetic variants in pheochromocytoma/paraganglioma: single-center experience.

Endocr Oncol

Department of Medicine, Division of Endocrinology and Metabolism, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Published: January 2023

AI Article Synopsis

  • - Pheochromocytoma and paragangliomas (PPGLs) are rare tumors linked to hereditary genetic variants in about 25-40% of cases; a study evaluated 115 patients to understand their genetic profiles and clinical characteristics.
  • - Out of the patients tested, 67 (58.3%) had gene variants related to PPGL, with some having exclusively pathogenic variants and others with variants of uncertain significance; key genes identified included RET and SDHB.
  • - A Clinical Judgment Score (CJS) was developed to predict which patients might not need genetic testing, demonstrating high sensitivity and specificity, which could optimize care and reduce costs for patients at lower risk.

Article Abstract

Pheochromocytoma and paragangliomas (PPGLs) are rare neuroendocrine tumors carrying 25-40% pathogenic germline gene variants (PGVs). We evaluated clinical, laboratory, and germline molecular profile of 115 patients with pathologic (14 patients were relatives from 8 different families recruited for genetic survey) confirmed PPGL followed in our institution. Patients with classic MEN2A/MEN2B phenotypes and at-risk relatives underwent direct analysis of proto-oncogene, and the remaining had samples submitted to complete next-generation sequencing aiming 23 PPGL-related genes: and . We also developed a clinical judgment score (CJS) to determine the probability of patients having a potentially hereditary disease. The resulting genetic landscape showed that 67 patients (58.3%) had variants in at least one gene: 34 (50.7%) had exclusively pathogenic or likely pathogenic variants, 13 (19.4%) had pathogenic or likely pathogenic variants and variant of undetermined significance (VUS), and 20 (29.8%) carried only VUS. PGVs were found in ( = 18; 38.3%), ( = 10; 21.3%), and ( = 8; 17% each), and , , and ( = 1; 2.1% each). Direct genetic testing disclosed 91.3% sensitivity, 81.2% specificity, and 76.4% and 93.3% positive predictive value (PPV) and negative predictive values (NPV), respectively. The CJS to identify patients who would not benefit from genetic testing had 75% sensitivity, 96.4% specificity, and 60% and 98.2% PPV and NPV, respectively. In summary, the landscape of PPGL germline gene variants from 115 Brazilian patients resulted in slightly higher prevalent pathogenic and likely pathogenic variants, especially in the gene. We suggest a CJS to identify PPGL patients who would not require initial genetic evaluation, improving test specificity and reducing costs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388674PMC
http://dx.doi.org/10.1530/EO-22-0091DOI Listing

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