ArticleNeuroendocrinology2025
Circulating Tumor DNA Profiling Identifies Actionable Mutations as Prognostic Markers in Advanced Neuroendocrine Tumors.
Article in Neuroendocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Inter- and intra-quartile comparison of multi-tracer PET/CT and liquid biopsy molecular markers in cancer: a futuristic perspective on evolving a "stepped care" model for individualized precision theranostics through AI/ML.European journal of nuclear medicine and molecular imaging · 2026Article
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11 authors.
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Abstract
<p>Introduction: Neuroendocrine tumors (NETs) are a rare and heterogeneous group of neoplasms with both clinical and genetic diversity. The clinical applicability of molecular profiling using liquid biopsy for identifying actionable drug targets and prognostic indicators in patients with advanced NETs remains unclear.
methodsIn this study, we utilized a custom-made 37 genes panel of circulating tumor DNA (ctDNA) based on next-generation sequencing in 47 patients with advanced NETs.
resultsA total of 223 non-synonymous mutations were identified, with the highest frequencies found in TSC2, JAG2, NOTCH3, KMT2C, and SETD2. NETs originating from the stomach exhibited the highest average mutation frequency, while paragangliomas had the lowest. TERT mutations were associated with significantly higher hazard ratios for both progression-free survival (PFS) and overall survival (OS). Higher blood tumor mutational burden (bTMB) was linked to poor prognosis in octreotide LAR-treated patients and correlated with higher Ki-67 levels and alterations in the TM, mTOR, and Notch pathways. Treatment responders had higher bTMB, chromatin remodeling signaling mutation burden, and maximum somatic allele frequency (MSAF). Patients with high MSAF demonstrated better PFS, whereas those with low MSAF had better OS. A strong positive correlation was observed between MSAF levels and mutational burden. Co-occurring mutations in the TM, mTOR, and NOTCH pathways suggested future therapeutic strategies.
conclusionsWe constructed an overview of mutations in 37 genes, linking ctDNA to survival in advanced NETs. TERT mutations, bTMB, and MSAF predict PFS or OS. Co-occurring TM, mTOR, and NOTCH pathway alterations highlight ctDNA's potential in guiding precision medicine. </p>.
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