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SJ Klempner, B Gershenhorn, P Tran, TK Lee, MG Erlander, K Gowen, AB Schrock, D Morosini, JS Ross, VA Miller, PJ Stephens, SI Ou and SM Ali
Abstract
Neuroendocrine tumors comprise a heterogeneous group of malignancies with a broad spectrum of clinical behavior. Poorly differentiated tumors follow an aggressive course with limited treatment options, and new approaches are needed. Oncogenic BRAF V600E (BRAFV600E) substitutions are observed primarily in melanoma, colon cancer, and non-small cell lung cancer, but have been identified in multiple tumor types. Here we describe the first reported recurrent BRAFV600E mutations in advanced high grade colorectal neuroendocrine tumors, and identify BRAF alteration frequency of 9% in 108 cases. Among these BRAF alterations 80% were BRAFV600E. Dramatic response to BRAF-MEK combination occurred in two cases of metastatic high grade rectal neuroendocrine carcinoma refractory to standard therapy. Urinary BRAFV600E circulating tumor DNA monitoring paralleled disease response. Our series represents the largest study of genomic profiling in colorectal neuroendocrine tumors and provides strong evidence that BRAFV600E is an oncogenic driver responsive to BRAF/MEK combination therapy in this molecular subset.
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Concepts
Non-small cell lung carcinoma, Colon, Colorectal cancer, Tumor, Metastasis, Oncology, Lung cancer, Cancer
MeSH headings
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