SDHAF2 (Succinate Dehydrogenase Complex Assembly Factor 2)

As FLCN and SDH are not currently included in the current guidelines for EO-CRC, PVs/LPVs in these genes may be underestimated. To better understand their significance, we recommend including their assessment in all patients with EO-CRC.

This case highlights an unusual clinical course: a carotid body paraganglioma, initially asymptomatic and successfully resected, developed skeletal metastasis after a prolonged disease-free interval of 7 years. This report underscores the importance of revisiting conventional risk stratification, incorporating genetic testing, and ensuring vigilant, long-term follow-up.

Surgical treatment was performed in 67.3% of cases, and systemic radiotherapy was utilized in advanced cases, achieving stable disease in most cases. In this largest Indian cohort of SDHx PPGL, high metastatic burden, SDHB dominance, and novel gene variants were noted.

Our study highlights the variability in PPGL-associated mutation carrier prevalence across genes and ancestries. The findings underscore potential disparities in genetic risk that may not have been fully captured by clinical cohorts.

Considering the implications of SDH function in both normal physiology and disease, understanding SDH function has fundamental and translational implications. This review seeks to summarize SDH deficiency, focusing on the role SDH plays in metabolism, the metabolic consequences of SDH deficiency, the proteomic consequences of SDH loss, thereby highlight potential therapeutic vulnerabilities in SDH-deficient cells.

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2025 --> Mar 2026 | Trial primary completion date: Sep 2025 --> Mar 2026

In this review, we provide a brief up-to-date clinical overview of HPPS and describe recently proposed tumor surveillance regimens. We then detail our updated consensus pediatric-focused tumor surveillance recommendations from the 2023 AACR Childhood Cancer Predisposition Workshop.

This work elucidated the potential tissue adaptation mechanism of intratumoral dynamic interactions between MES-GBM cells, MDMs and T cells in anti-PD-1 non-responders and identified the therapeutic potential of targeting ITGA5 to reduce anti-PD-1 resistance in GBM.

The current study offers new insights into the phenotypic characterisation of SDHAF2-related paraganglioma syndrome including the development of extra-cervical PGLs and metastatic transformation.

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2025 --> Sep 2025 | Trial primary completion date: Feb 2025 --> Sep 2025

These findings highlight similarities and differences in the cellular response to SDH loss between the two cell models. We show that adrenally-derived cells display more severe morphological cellular and mitochondrial alterations, yet are unique in preserving residual Complex I function, perhaps allowing them to better tolerate SDH loss, thus making them a closer model to SDH-loss PPGL relative to fibroblasts.(281 words).

This has expanded the catalog of tumor driver genes, which are identifiable in up to 70% of patients Integrated genomic and transcriptomic data over the last 10 years have revealed three distinct major molecular signatures, triggered by pathogenic variants in susceptibility genes and characterized by the activation of a specific oncogenic signaling: the pseudo hypoxic, the kinase, and the Wnt signaling pathways. These molecular clusters show a different biochemical phenotype and clinical behavior; they may also represent the prerequisite for implementing customized therapy and follow-up.