title: Establishment and Characterization of a Novel Cell Line, ASAN-PaCa, Derived From Human Adenocarcinoma Arising in Intraductal Papillary Mucinous Neoplasm of the Pancreas.
abstract: Our aim was to establish and characterize a novel pancreatic ductal adenocarcinoma cell line from a patient in whom the origin of the invasive carcinoma could be traced back to the intraductal papillary mucinous neoplasm (IPMN) precursor lesion.
  
  
  
  The primary patient-derived tumor was propagated in immunocompromised mice for 2 generations and used to establish a continuous in vitro culture termed ASAN-PaCa. Transplantation to fertilized chicken eggs confirmed the tumorigenic potential in vivo. Molecular analyses included karyotyping, next-generation genomic sequencing, expression analysis of marker proteins, and mucin-profiling.
  
  
  
  The analysis of marker proteins confirmed the epithelial nature of the established cell line, and revealed that the expression of the mucin MUC1 was higher than that of MUC2 and MUC5AC. ASAN-PaCa cells showed rapid in vitro and in vivo growth and multiple chromosomal aberrations. They harbored mutations in KRAS (Q61H), TP53 (Y220C), and RNF43 (I47V and L418M) but lacked either IPMN-specific GNAS or presumed pancreatic ductal adenocarcinoma-driving mutations in KRAS (codons 12/13), SMAD, and CDKN2A genes.
  
  
  
  ASAN-PaCa cell line represents a novel preclinical model of pancreatic adenocarcinoma arising in the background of IPMN, and offers an opportunity to study how further introduction of known driver mutations might contribute to pancreatic carcinogenesis.
authors: From the *Department of Surgery, University Hospital Heidelberg; †Infection and Cancer Program, Tumor Virology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany; ‡Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France; §Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ); ∥Institute of Human Genetics, Cytogenetic, University Hospital Heidelberg; ¶Molecular OncoSurgery Group, Department of General and Transplantation Surgery, University of Heidelberg and German Cancer Research Center; and Institutes of #Immunology, and **Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors: Anette
authors: A
authors: Heller
authors: Assia L
authors: AL
authors: Angelova
authors: Sonja
authors: S
authors: Bauer
authors: Svitlana P
authors: SP
authors: Grekova
authors: Marc
authors: M
authors: Aprahamian
authors: Jean
authors: J
authors: Rommelaere
authors: Michael
authors: M
authors: Volkmar
authors: Johannes W G
authors: JW
authors: Janssen
authors: Nathalie
authors: N
authors: Bauer
authors: Ingrid
authors: I
authors: Herr
authors: Thomas
authors: T
authors: Giese
authors: Matthias M
authors: MM
authors: Gaida
authors: Frank
authors: F
authors: Bergmann
authors: Thilo
authors: T
authors: Hackert
authors: Stefan
authors: S
authors: Fritz
authors: Nathalia A
authors: NA
authors: Giese
mesh_terms: D000230:Adenocarcinoma; D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D055262:Mucin-2; D010190:Pancreatic Neoplasms
chemical_list: D055262:Mucin-2