| Literature DB >> 34326338 |
Job van Riet1,2,3, Harmen J G van de Werken4,5, Edwin Cuppen6,7, Ferry A L M Eskens3, Margot Tesselaar8, Linde M van Veenendaal8, Heinz-Josef Klümpen9, Marcus W Dercksen10, Gerlof D Valk11, Martijn P Lolkema3,12, Stefan Sleijfer3,12, Bianca Mostert13.
Abstract
Metastatic and locally-advanced neuroendocrine neoplasms (aNEN) form clinically and genetically heterogeneous malignancies, characterized by distinct prognoses based upon primary tumor localization, functionality, grade, proliferation index and diverse outcomes to treatment. Here, we report the mutational landscape of 85 whole-genome sequenced aNEN. This landscape reveals distinct genomic subpopulations of aNEN based on primary localization and differentiation grade; we observe relatively high tumor mutational burdens (TMB) in neuroendocrine carcinoma (average 5.45 somatic mutations per megabase) with TP53, KRAS, RB1, CSMD3, APC, CSMD1, LRATD2, TRRAP and MYC as major drivers versus an overall low TMB in neuroendocrine tumors (1.09). Furthermore, we observe distinct drivers which are enriched in somatic aberrations in pancreatic (MEN1, ATRX, DAXX, DMD and CREBBP) and midgut-derived neuroendocrine tumors (CDKN1B). Finally, 49% of aNEN patients reveal potential therapeutic targets based upon actionable (and responsive) somatic aberrations within their genome; potentially directing improvements in aNEN treatment strategies.Entities:
Year: 2021 PMID： 34326338 PMCID： PMC8322054 DOI： 10.1038/s41467-021-24812-3
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919