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Only one NET G3 patient harbored a TP53 mutation compared to 33 NEC, and NET G3 contained fewer oncogenic mutations compared to the NEC profiles. 45 patients had somatic mutations in 61 selected different cancer associated genes and 23 patients were TMB-high (>10 mutations/mega base). 

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Enhancing Treatment Strategies for Metastatic High-Grade Neuroendocrine Neoplasms

High-grade neuroendocrine neoplasms (HG-NEN) including neuroendocrine carcinoma (NEC) and high-grade neuroendocrine tumors (NET G3) is a heterogenous group of rare cancers characterized by rapid growth and poor prognosis. The therapeutic options for HG-NEN are limited and the molecular characterization of the patient population is not well-investigated. We report the potential of extensive genomic profiling to inform on treatment of metastatic HG-NEN. 

49 patients with metastatic HG-NEN and exhausted therapeutic options underwent Whole-Exome Sequencing (WES) or Whole-Genome Sequencing (WGS) upon referral to the Phase 1 Unit. We found that NEC and NET G3 appeared molecularly distinct  i.e., only one NET G3 patient was TP53 mutated compared to 33 NEC and NET G3 contained fewer oncogenic mutations compared to the NEC profiles. 45 patients had somatic mutations in 61 selected different cancer associated genes and 23 patients were TMB-high defined as >10 mutations per mega base. In total 49% of the patients presented with actionable genomic variants. In conclusion, extensive genomic profiling in pts with HG-NEN holds potential extending therapeutic options.