Background and objectives: The World Health Organization (WHO) 2010 has classified GI neuroendocrine neoplasms into neuroendocrine tumor (NET) and high-grade neuroendocrine carcinoma (NEC). The genetic underpinnings of NEC are poorly understood. The aim of the study was to perform genomic profiling of NEC to better characterize this aggressive disease.
Methods: We identified nine patients with colonic NEC between January 1, 2005 and June 30, 2013. Whole exome sequencing (WES) was performed on tumor DNA from two patients with ≥80% tumor cellularity and matched normal tissue available. Focused BRAF mutational analysis was performed on an additional seven patients via sanger sequencing of BRAF exons 11 and 15.
Results: We identified BRAF exon 15 mutations (c.A1781G: p.D594G and c.T1799A: p.V600E) by WES in two patients. Upon additional screening of seven colonic NECs for BRAF exon 11 and 15 mutations, we identified BRAF V600E mutations in two of seven specimens (29%). Overall, BRAF exon 15 mutations were present in four of nine colonic NECs.
Conclusion: Colonic NEC is a rare but aggressive tumor with high frequency (44%) of BRAF mutations. Further investigation is warranted to ascertain the incidence of BRAF mutations in a larger population as BRAF inhibition may be a potential avenue of targeted treatment for these patients.
Keywords: BRAF; carcinoma; gastrointestinal; high grade; neuroendocrine; poorly-differentiated.
© 2017 Wiley Periodicals, Inc.