Gastroenterology

Gastroenterology

Volume 151, Issue 2, August 2016, Pages 267-270
Gastroenterology

Original Research
Brief Report
Detection of Hot-Spot Mutations in Circulating Cell-Free DNA From Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas

https://doi.org/10.1053/j.gastro.2016.04.034Get rights and content

Intraductal papillary mucinous neoplasms (IPMNs) are the most frequent cystic pancreatic tumors. Little is known about their molecular alterations, but mutations in GNAS have been reported to promote IPMN formation. A tumor-derived fraction of circulating cell-free DNA (cfDNA), isolated from blood samples, contains many of the same mutations as the primary tumor, and could be a tool for noninvasive disease monitoring. We found that the total amount of cfDNA can discriminate between individuals without pancreatic lesions (controls) and patients with Fukuoka-negative branch-duct IPMN or pancreatic cancer. Furthermore, we detected GNAS mutations in cfDNA from patients with IPMN, but not in patients with serous cystadenoma or controls. Analyses of cfDNA might therefore be used in the diagnosis of patients with IPMN or in monitoring disease progression.

Section snippets

Study Population

In this retrospective study, the following 5 cohorts were analyzed (Supplementary Tables 1–4 and 6): 21 IPMN patients (blood; IPMN surveillance); 38 healthy controls (blood; control); 24 patients with metastatic PDAC (blood; PDAC); 26 patients with resected SCA (blood; SCA); and 16 patients with borderline IPMN (blood/tissue; IPMN resected).

Cell-Free DNA Levels

IPMN patients showed a mean cfDNA value of 0.2887 ± 0.0319 ng/μL, controls had significantly less cfDNA with 0.1360 ± 0.0203 ng/μL (P < .001) (Figure 1A,

Discussion

Our main findings are that cfDNA discriminates IPMN patients from controls, but also from metastatic PDAC; cfDNA allows targeted genotyping for known driver mutations, even in benign pancreatic lesions; and the detection of GNAS and KRAS mutations allow discriminating IPMN patients from those with per se harmless pancreatic tumors, such as SCA.

Recent studies reported on the diagnostic potential of cfDNA quantification in benign and malignant pulmonary9, 10 and colorectal diseases.11 In the

Acknowledgments

The authors wish to thank Nathalia A. Giese, MD from the PancoBank platform (Biobank at the European Pancreas Centre at Heidelberg University Hospital), Mrs Magdalena Bienek-Ziolkowski and Mrs Rosina Sing (Biobank, Department of Internal Medicine I, Ulm University) for excellent technical assistance.

Thomas Seufferlein and Alexander Kleger contributed equally and jointly supervised this work.

References (14)

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Conflicts of interest The authors disclose no conflicts.

Funding This study was funded by the Deutsche Forschungsgemeinschaft (DFG, K.L. 2544/1-1 and 1-2), the Forschungskern SyStaR to Alexander Kleger, BIU (Böhringer Ingelheim Ulm to Alexander Kleger), the Else-Kröner-Fresenius-Stiftung (2011_A200), a German Cancer Aid Max Eder Fellowship to Patrick C. Hermann, a German Cancer Aid Grant to A.K. (111879), the Fritz-Thyssen Foundation to Alexander Kleger (2015-00363) and the Hector Foundation Cancer Research Fund to Patrick C. Hermann. Alexander Klegeris indebted to the Baden-Württemberg Stiftung for the financial support of this research project by the Eliteprogramme for Postdocs. Alexander Kleger is also an Else-Kröner-Fresenius Memorial Fellow. This work was also supported by the Interdisciplinary Center for Clinical Research (IZKF Aachen), RWTH Aachen University Medical School, Aachen, Germany to Ivan G. Costa and by BMBF grants (01GS08114, 01ZX1305C, and 01KT1506), Heidelberger Stiftung Chirurgie and Biomaterial Bank Heidelberg (BMBF grant 01EY1101) for Markus W. Büchler.

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