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Vijayvergia N , Boland PM , Handorf E , Gustafson KS , Gong Y , Cooper HS , Sheriff F , Astsaturov I , Cohen SJ , Engstrom PF
Molecular profiling of neuroendocrine malignancies to identify prognostic and therapeutic markers: a Fox Chase Cancer Center Pilot Study
Br J Cancer. 2016 Aug 23;115(5) :564-70
PMID: 27482646 PMCID: PMC4997552 URL: http://www.ncbi.nlm.nih.gov/pubmed/27482646
AbstractBACKGROUND: The rarity of neuroendocrine malignancies limits the ability to develop new therapies and thus a better understanding of the underlying biology is critical. METHODS: Through a prospective, IRB-approved protocol, patients with neuroendocrine malignancies underwent next-generation sequencing of their tumours to detect somatic mutations (SMs) in 50 cancer-related genes. Clinicopathologic correlation was made among poorly differentiated neuroendocrine carcinomas (NECs/poorly differentiated histology and Ki-67 >20%) and pancreatic neuroendocrine tumours (PanNETs/Ki67 20%) and non-pancreatic neuroendocrine tumours (NP-NETs/Ki67 20%). RESULTS: A total of 77 patients were enrolled, with next-generation sequencing results available on 63 patients. Incidence of SMs was 83% (19 out of 23) in poorly differentiated NECs, 45% (5 out of 11) in PanNETs and 14% (4 out of 29) in NP-NETs. TP53 was the most prevalent mutation in poorly differentiated NECs (57%), and KRAS (30%), PIK3CA/PTEN (22%) and BRAF (13%) mutations were also found. Small intestinal neuroendocrine tumours (Ki67 <2%/n=9) did not harbour any mutations. Prevalence of mutations correlated with higher risk of progression within the previous year (32% (low risk) vs 11% (high risk), P=0.01) and TP53 mutation correlated with worse survival (2-year survival 66% vs 97%, P=0.003). CONCLUSIONS: Poorly differentiated NECs have a high mutation burden with potentially targetable mutations. The TP53 mutations are associated with poor survival in neuroendocrine malignancies. These findings have clinical trial implications for choice of therapy and prognostic stratification and warrant confirmation.
NotesVijayvergia, Namrata Boland, Patrick M Handorf, Elizabeth Gustafson, Karen S Gong, Yulan Cooper, Harry S Sheriff, Fathima Astsaturov, Igor Cohen, Steven J Engstrom, Paul F England Br J Cancer. 2016 Aug 23;115(5):564-70. doi: 10.1038/bjc.2016.229. Epub 2016 Aug 2.