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IPMNs with co-occurring invasive cancers: neighbours but not always relatives
  1. Matthäus Felsenstein1,2,
  2. Michaël Noë1,
  3. David L Masica3,4,
  4. Waki Hosoda1,
  5. Peter Chianchiano1,
  6. Catherine G Fischer1,
  7. Gemma Lionheart1,
  8. Lodewijk A A Brosens5,
  9. Antonio Pea6,
  10. Jun Yu7,
  11. Georgios Gemenetzis7,
  12. Vincent P Groot7,8,
  13. Martin A Makary7,
  14. Jin He7,
  15. Matthew J Weiss7,
  16. John L Cameron7,
  17. Christopher L Wolfgang7,
  18. Ralph H Hruban1,9,
  19. Nicholas J Roberts1,
  20. Rachel Karchin3,4,
  21. Michael G Goggins1,9,
  22. Laura D Wood1,9
  1. 1Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  2. 2Department of Surgery, Charité—Universitätsmedizin Berlin, Berlin, Germany
  3. 3Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  4. 4Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA
  5. 5Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  6. 6Department of Surgery, University and Hospital Trust of Verona, Verona, Italy
  7. 7Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  8. 8Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
  9. 9Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Dr Laura D Wood, Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; ldwood{at}


Objective Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated.

Design We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient.

Results We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes.

Conclusion This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.

  • pancreatic cancer
  • mutations
  • cancer genetics
  • molecular genetics
  • carcinogenesis

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  • Contributors MF and LDW designed the study. MF, MN, PC, CGF, GL, LAAB, AP, JY, GG, VPG, MAM, JH, MJW, JLC and CLW collected data. MF, MN, DLM, WH, RHH, NJR, RK, MGG and LDW analysed and interpreted data. MF and LDW wrote the paper. All authors contributed to critical revision and approved of the final version.

  • Funding The authors acknowledge the following sources of support: NIH/NCI P50 CA62924; NIH/NIDDK K08 DK107781; Sol Goldman Pancreatic Cancer Research Center; DFG-German Research Foundation; Buffone Family Gastrointestinal Cancer Research Fund; Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention; AGA-Bernard Lee Schwartz Foundation Research Scholar Award in Pancreatic Cancer; Sidney Kimmel Foundation for Cancer Research Kimmel Scholar Award; AACR-Incyte Corporation Career Development Award for Pancreatic Cancer Research; Rolfe Pancreatic Cancer Foundation; Joseph C Monastra Foundation; The Gerald O Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees); Dutch Digestive Foundation (CDG 14-02); The Lisa Waller Hayes Foundation; The Nijbakker-Morra Foundation.

  • Competing interests LDW is a paid consultant for Personal Genome Diagnostics. The other authors declare no competing interests.

  • Ethics approval Johns Hopkins Hospital Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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