Identification of molecular markers specific for pancreatic neuroendocrine tumors by genetic profiling of core biopsies.
BACKGROUND
There is a paucity of known molecular markers that distinguish pancreatic neuroendocrine tumors from other pancreatic tumor types. We hypothesized that novel markers for pancreatic neuroendocrine tumors could be identified with molecular fingerprinting of pooled RNA samples from core biopsies.


METHODS
Total RNA was harvested from nine core biopsies of normal pancreas, pancreatitis, pancreatic adenocarcinoma, pancreatic adenocarcinoma metastases, and pancreatic neuroendocrine tumors. RNA from each group of samples was pooled and hybridized to an oligonucleotide-based microarray. Four genes (ANG2, NPDC1, ELOVL4, and CALCR) were selected for further investigation by reverse transcriptase polymerase chain reaction from the top 20 highest expressed genes, on the basis of potential as novel markers.


RESULTS
Neuroendocrine tumors were most unique from normal pancreas. Pancreatitis, pancreatic adenocarcinoma, and metastases are more closely related to each other and to normal pancreas. ANG2 was overexpressed in 89% of neuroendocrine tumors, compared with 22% of normal pancreas, making it the best potential molecular marker or therapeutic target of the four genes selected for analysis.


CONCLUSIONS
We have identified a specific set of molecular markers for pancreatic neuroendocrine tumors distinct from pancreatitis and pancreatic adenocarcinoma. These novel markers may prove useful as molecular markers or therapeutic targets unique to pancreatic neuroendocrine tumors.
Bloomston
Mark
M
Surgery, Moffitt Cancer Center, Tampa, Florida 33612, USA.
Durkin
Alan
A
Yang
Ivana
I
Rojiani
Mumtaz
M
Rosemurgy
Alexander S
AS
Enkmann
Steven
S
Yeatman
Timothy J
TJ
Zervos
Emmanuel E
EE
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012334:RNA, Neoplasm / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm