Original ResearchBrief ReportDetection of Hot-Spot Mutations in Circulating Cell-Free DNA From Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas
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.
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Cited by (72)
Blood-Based Biomarkers in the Diagnosis and Risk Stratification of Pancreatic Cysts
2023, Gastrointestinal Endoscopy Clinics of North AmericaBlood biomarkers for differential diagnosis and early detection of pancreatic cancer
2021, Cancer Treatment ReviewsCitation Excerpt :Still, mutational analysis of ctDNA could contribute diagnostic value together with other marker molecules (see mixed panel section below), but may be better suited to provide prognostic information and allow disease monitoring. In a rather different approach, it was reported that simply the amount of ctDNA isolated from plasma samples was able to discriminate PDAC from control samples, irrespective of the ctDNA’s mutational status [56–58], although it is unclear how specific this may be. Analyses of ctDNA work at the detection limit [54] and ctDNA amounts are higher in patients with a larger tumor volume and metastases [59].
Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application
2021, PancreatologyCitation Excerpt :Recently, studies have also demonstrated a significant correlation between the detection of mutant KRAS ctDNA at pre-treatment sampling and the presence of liver metastases in patients, indicating potential tissue-specific patterns between ctDNA release from primary and metastatic lesions, which warrant further assessment [20]. The analysis of ctDNA can also provide a useful tool for the early diagnosis of PDAC tumours, when surgical resection is most likely to improve survival [31,32,45,76–80]. In a sample cohort of 221 resectable (stage I-II) PDAC patients, KRAS mutant ctDNA was detected in 30% of cases, with 94% of mutations present within codon 12 and a further 6% within codon 61 [31].
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.
Author names in bold designate shared co-first authorship.
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Authors share co-first authorship.
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Authors share co-senior authorship.