Epigenetic signatures may help detect and differentiate small intestinal neuroendocrine tumors (SINETs) from other tumor types, according to findings (NET Abstract #BT6) presented at the 7th Annual Neuroendocrine Tumors (NET) conference in Nashville, TN. The meeting was organized by the North American Neuroendocrine Tumors Society (NANETS).
Hypermethylation of the gastric inhibitory polypeptide receptor gene (GIPR) was seen in 92% of SINET tumors’ DNA, the authors reported.
“This study is the first comprehensive analysis of the epigenetic profile of SINET and identifies hypermethylation of GIPR as a potential novel biomarker,” reported lead study author Anna Karpathakis of University College London Cancer Institute, in London, England, and her coauthors.
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“Novel radioligands targeting GIPR have been developed for use as imaging tools,” they noted, suggesting that their availability helps to make GIPR a promising target for the development of targeted therapies.
Little is known about the role of methylation epigenetics in SINET pathogenesis, Dr. Karpathakis noted. The team utilized the Infinium HumanMethylation450 Array to analyze DNA from 49 SINET primary tumors and 21 normal small intestine biopsies.
Their analysis found 11 candidate biomarker genes for SINET, which were found to exhibit altered methylation and expression. These candidate genes include downregulated CDX1, FBP1, GATA5, and C20orf54, and upregulated GIPR, PTPRN, PCSK1, PRLHR, CELSR3, SCGN, and LMX1B.
In addition, GIPR hypermethylation was found to be “sensitive for the detection of SINET compared to other GI malignancies with an [area under the curve] of 0.991 (99% CI: 0.991-0.999),” the coauthors reported.
