title: Genomic Characterization of Low- and High-Grade Pancreatic Mucinous Cystic Neoplasms Reveals Recurrent KRAS Alterations in "High-Risk" Lesions.
abstract: Pancreatic ductal adenocarcinoma arises from the following 3 distinct precursor lesions: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm (MCN). Genetic abnormalities in the first 2 precursor lesions have been well characterized, but there are limited data on progression pathways in MCNs. This study aimed to characterize genomic differences between MCNs with low-grade (LG) and high-grade (HG) dysplasia or carcinoma.
  
  
  
  Neoplastic epithelium from surgical resections of 25 MCNs, 16 with LG dysplasia and 9 with HG dysplasia or invasive carcinoma, was analyzed by targeted massively parallel sequencing.
  
  
  
  KRAS mutations were most frequent, present in 9 HG (100%) and 3 LG (19%) tumors, 2 of the latter also having discrete areas of HG tumor with the same mutation. TP53 mutations and CDKN2A loss were identified in 5 HG tumors (56%) each but not in LG tumors.
  
  
  
  The low frequency of KRAS alterations in cysts without a HG component suggests that a subset of MCNs may have a low risk for malignant progression. Novel single-nucleotide variants that occur at a lower rate may help identify this group and provide a substrate for new diagnostic, prognostic, and therapeutic targets.
authors.affiliation: From the *Department of Pathology, Brigham and Women's Hospital; †Harvard Medical School; and ‡Department of Pathology, Massachusetts General Hospital, Boston, MA.
authors.forename: James R
authors.initials: JR
authors.lastname: Conner
authors.forename: Adrián
authors.initials: A
authors.lastname: Mariño-Enríquez
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garcia
authors.forename: Martha B
authors.initials: MB
authors.lastname: Pitman
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.forename: Amitabh
authors.initials: A
authors.lastname: Srivastava
authors.forename: Leona A
authors.initials: LA
authors.lastname: Doyle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012307:Risk Factors
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)