Genomic Profiling of Metastatic Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients in the Personalized-Medicine Era.
BACKGROUND
We have conducted molecular profiling through a high-throughput molecular test as part of our clinical practice for patients with advanced gastrointestinal (GI) cancer or rare cancers including gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Herein, we report on the molecular characterization of 14 metastatic GEP-NET patients.


METHODS
We conducted the Ion AmpliSeq Cancer Hotspot Panel v2 (detecting 2,855 oncogenic mutations in 50 commonly mutated genes) and nCounter Copy Number Variation Assay, which was designed with 21 genes based on available targeted agents, as a high throughput genomic platform in 14 patients with metastatic GEP-NETs.


RESULTS
Among the 14 GEP-NET patients analyzed in this study, 8 patients had grade III neuroendocrine carcinoma (NEC) and 6 had grade I/II NET. Primary sites included pancreas (n=3), small intestine and ascending colon (n=3), distal colon and rectum (n=5), and unknown primary origin (n=3). The most common metastatic site was the liver. Of 14 GEP-NET patients available for mutational profiling, 7 (50.0%) patients had one or more aberrations detected. Common aberrations were as follows: SMARCB1 mutation (n=2), TP53 mutation (n=2), STK11 mutation (n=1), RET mutation (n=1), and BRAF mutation (n=1). Gene amplification by nCounter was detected in only 1 patient, showing CCNE1 amplification, and this patient also had a TP53 mutation.


CONCLUSIONS
This high throughput genomic test may be useful to identify new drug targets in metastatic GEP-NET patients. Currently, we plan to conduct further genomic analysis to develop predictive and prognostic biomarkers in a larger number of GEP-NET patients.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seung Tae
ST
Kim
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Su Jin
SJ
Lee
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Se Hoon
SH
Park
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Joon Oh
JO
Park
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ho Yeong
HY
Lim
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Won Ki
WK
Kang
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jeeyun
J
Lee
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young Suk
YS
Park
Gastroenteropancreatic neuroendocrine tumor (GEP-NET); molecular profiling