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Novel DNA markers identify advanced neoplasia in pancreatic cysts
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LAS VEGAS — Novel methylation DNA markers accurately identified advanced neoplasia in patients with pancreatic cysts, according to findings presented at ACG 2016.
Shounak Majumder, MD, of Mayo Clinic, Jacksonville, Fla., and colleagues conducted a blinded multicenter study where they identified pancreatic cyst fluid in 83 surgically resected cysts from 14 patients with high-grade dysplasia (HGD; n = 4) or adenocarcinoma (n = 10) and 61 controls with low-grade dysplasia or no dysplasia. The researchers extracted DNA from 0.2 mL of cyst fluid, which was then bisulfite converted. Then they performed an assay via methylation specific polymerase chain reaction.
Shounak Majumder
Majumder said during his presentation that the DNA methylation markers have multiple benefits: they provide a single predictable target site, markers are highly informative and are readily available assay platforms.
“We chose to explore this class of markers [that discriminates HGD or adenocarcinoma from low-grade dysplasia] and presented it at DDW this year. We identified and validated a panel of novel methylated DNA markers,” Majumder said. “[However,] it remains to be determined if this discrimination in tissue applies to cyst fluid. The aim was to assess and compare the distribution of methylated DNA markers in cyst fluid that distinguish between high-grade dysplasia or cancer and low-grade dysplasia.”
The top 10 markers that distinguished between patients with HGD and cancer with controls were: BMP3, EMX1, CLEC11A, VWC2, ST8SIA1, PRK CB, TRX15, ELMO-1, LRRC4S and CD1D. The top five markers were BMP3, EMX1, CLEC11A, ST8IA1 and VWC2, and reached areas under the receiving curve (AUC) of more than 0.9 when distinguishing the cases from controls.
“Cases with high-grade dysplasia and cancer demonstrate a many-fold higher level compared to cysts with no dysplasia and is consistent across top three markers,” Majumder said.
When two markers combined, the performance increased further, according to Majumder. A combination provides an AUC of 0.96, which translates to a sensitivity of 95% and specificity of 90%. The Fukuoka guidelines are lower, Majumder said.
Majumder concluded: “In pancreatic cyst fluid, novel methylated DNA markers accurately discriminate cases from controls. “[They] have potential to improve identification of cysts at higher malignant risk.” – by Melinda Stevens
Reference:
Majumder S, et al. Abstract #55. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 14-19, 2016; Las Vegas, NV.
Disclosure: Multiple researchers report having patent and stock holdings in Exact Sciences.
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