PMID- 28940307
OWN - NLM
STAT- MEDLINE
DCOM- 20180306
LR  - 20180306
IS  - 1096-9098 (Electronic)
IS  - 0022-4790 (Linking)
VI  - 117
IP  - 2
DP  - 2018 Feb
TI  - Frequent BRAF mutations suggest a novel oncogenic driver in colonic
      neuroendocrine carcinoma.
PG  - 284-289
LID - 10.1002/jso.24834 [doi]
AB  - 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.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Idrees, Kamran
AU  - Idrees K
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
AD  - Division of Oncology and Endocrine Surgery, Vanderbilt University Medical Center,
      Nashville, Tennessee.
FAU - Padmanabhan, Chandrasekhar
AU  - Padmanabhan C
AUID- ORCID: http://orcid.org/0000-0002-8715-1703
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Liu, Eric
AU  - Liu E
AD  - Rocky Mountain Cancer Centers, Denver, Colorado.
FAU - Guo, Yan
AU  - Guo Y
AD  - Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee.
FAU - Gonzalez, Raul S
AU  - Gonzalez RS
AD  - Department of Pathology and Laboratory Medicine, University of Rochester,
      Rochester, New York.
FAU - Berlin, Jordan
AU  - Berlin J
AD  - Department of Medicine (Hematology/Oncology), Vanderbilt University Medical
      Center, Nashville, Tennessee.
FAU - Dahlman, Kimberly B
AU  - Dahlman KB
AD  - Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee.
FAU - Beauchamp, R Daniel
AU  - Beauchamp RD
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
AD  - Division of Oncology and Endocrine Surgery, Vanderbilt University Medical Center,
      Nashville, Tennessee.
AD  - Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee.
FAU - Shi, Chanjuan
AU  - Shi C
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University
      Medical Center, Nashville, Tennessee.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - R01 CA158472/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170920
PL  - United States
TA  - J Surg Oncol
JT  - Journal of surgical oncology
JID - 0222643
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinogenesis/genetics/*pathology
MH  - Case-Control Studies
MH  - Colonic Neoplasms/genetics/*pathology
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neuroendocrine Tumors/genetics/*pathology
MH  - Prognosis
MH  - Proto-Oncogene Proteins B-raf/*genetics
OTO - NOTNLM
OT  - BRAF
OT  - carcinoma
OT  - gastrointestinal
OT  - high grade
OT  - neuroendocrine
OT  - poorly-differentiated
EDAT- 2017/09/25 06:00
MHDA- 2018/03/07 06:00
CRDT- 2017/09/24 06:00
PHST- 2017/02/28 00:00 [received]
PHST- 2017/08/17 00:00 [accepted]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2017/09/24 06:00 [entrez]
AID - 10.1002/jso.24834 [doi]
PST - ppublish
SO  - J Surg Oncol. 2018 Feb;117(2):284-289. doi: 10.1002/jso.24834. Epub 2017 Sep 20.