One genotype, many phenotypes: SDHB p.R90X mutation-associated paragangliomas

Alzahrani, Ali S.; Alswailem, Meshael; Moria, Yosra; Aldeheshi, Ayman; Al‐Hindi, Hindi

doi:10.1007/s12020-020-02461-8

Cited by 2 publications

(1 citation statement)

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“…Our data set contained 2162 patients [ 14 ] who presented with PPGL and in whom a germline or somatic PV in a PPGL susceptibility gene from the cluster 1 or 2 branch was detected [ 11 , 12 , 15-79 ]. The overall percentage of females was 51.1% (1104/2162).…”

Section: Resultsmentioning

confidence: 99%

Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma

Richter,

Bechmann

2024

Journal of the Endocrine Society

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Context Sexual and ancestral differences in driver gene prevalence have been described in many cancers, but have not yet been investigated in pheochromocytoma and paraganglioma (PPGL). Objective This study aims to assess whether sex and ancestry influence prevalence of PPGL driver genes and clinical presentation. Methods We conducted a retrospective analysis of patients with PPGL considering studies from 2010 onwards that included minimal data of type of disease, sex, mutated gene, and country of origin. Additional features were recorded when available (age, tumor location, bilateral or multifocal, somatic or germline, and metastatic disease). Results We included 2162 patients from which 877 originated in Europe and 757 in Asia. Males presented more often with germline pathogenic variants (PVs) in genes activating hypoxia pathways (p=0.0006), had more often sympathetic paragangliomas (p=0.0005) and metastasis (p=0.0039). On the other hand, females with PPGLs due to MAX PVs were diagnosed later than males (p=0.0378) and developed more often metastasis (p=0.0497). European but not Asian females presented more often with PPGLs due to PVs in genes related to kinase signaling (p=0.0052), particularly RET and TMEM127. Contrary to experiences from Europe, Asian patients with PPGL due to PVs in kinase signaling genes NF1, HRAS, and FGFR1 showed a high proportion of sympathetic tumors, while European patients almost exclusively have adrenal tumors (p<0.005). Conclusions Personalized management of patients with PPGL might benefit from considering sexual and ancestral differences. Further studies with better clinically aligned cohorts from various origins are required to better dissect ancestral influences on PPGL development.

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