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Article summary:
1. Neuroendocrine neoplasms (NEN) are a heterogeneous and uncommon tumor type that can arise from neuroendocrine cells distributed throughout the body. They are currently classified into poorly differentiated neuroendocrine carcinomas (NEC) and more differentiated neuroendocrine tumors (NET), with further subdivisions based on primary site, grade, differentiation, histology, and functionality.
2. Previous genomic studies on NEN have shown relatively stable genomes with few commonly observed driver mutations and allelic imbalances associated with their primary tissue of origin. Genetic drivers of NET include CDKN1B, chromatin-remodeling genes, DNA-repair genes, mTOR-related genes, and the oxygen-sensing modulator VHL. NEC is associated with aberrations in TP53, RB1, MYC, CCND1, KRAS, PIK3CA/PTEN, and BRAF.
3. The current classification parameters for NEN do not sufficiently separate patients and tumors according to prognosis and response to therapy. Limited whole-exome sequencing (WES) and whole-genome sequencing (WGS) data are available for NEN due to the rarity of the disease. There is a high unmet need to better classify and understand these diverse tumors in order to develop more tailored therapeutic strategies.
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