IDDF2018-ABS-0163 Pancreatic juice mutation concentrations can help predict the grade of dysplasia in patients undergoing pancreatic surveillance
Year: 2018
Type: conference-abstract
Abstract: Background The measurement of mutations in pancreatic juice samples collected from the duodenum during endoscopic ultrasound (EUS) may improve the diagnostic evaluation of patients undergoing pancreatic surveillance. Our aim was to evaluate the accuracy of using pancreatic juice mutation concentrations to predict the presence and histologic grade of neoplasia in the pancreas. Methods Digital next-generation sequencing (NGS) of pancreatic juice DNA using a targeted 12-gene panel was performed on 67 patients undergoing pancreatic evaluation during EUS at Johns Hopkins Hospital including patients with pancreatic ductal adenocarcinoma, patients who subsequently underwent pancreatic resection for precursor lesions, patients undergoing surveillance for their familial/inherited susceptibility to pancreatic cancer, and normal pancreas disease controls. Results One hundred fifty-five unique somatic mutations were detected after filtering based on the in-house developed algorithm. The most commonly mutated genes after KRAS and GNAS were in descending order of prevalence in TP53, RNF43, SMAD4, ARID1A, CDKN2A, FWXB7 and TGFBR2. Pancreatic juice mutations were detected in all 14 cases with pancreatic cancer, 12 of 13 (92.3%) cases with suspected precancerous lesions, 23 of the 31 high-risk individuals (74.2%) and 4 of 9 disease controls with a normal pancreas. Patients with pancreatic cancer or high-grade dysplasia as their highest grade lesion had significantly higher pancreatic juice mutation concentrations than all other subjects (mean/s.d. digital NGS score; 46.6±69.7 vs. 6.2±11.6, p=0.02). Pancreatic juice mutation concentrations distinguished patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with a sensitivity, 72.2%, specificity, 89.4% (area under the curve, AUC 0.872). Mutant TP53/SMAD4 concentrations could distinguish patients with pancreatic cancer or high-grade dysplasia in their resection specimen, from all other subjects with 61.1% sensitivity, 95.7% specificity (AUC 0.819). Among 31 high-risk individuals under surveillance, 2 of the 3 individuals with most abnormal pancreatic juice mutation profiles also had the most abnormalities on pancreatic imaging. Conclusions Pancreatic juice mutation analysis using digital NGS has potential diagnostic utility in the evaluation of patients undergoing pancreatic surveillance.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2805556637