title: Molecular analysis of mucinous nonneoplastic cyst of the pancreas.
abstract: Although a mucinous nonneoplastic cyst (MNNC) of the pancreas is defined as a benign nonneoplastic lesion with no malignant potential, its histogenesis and etiology are still uncertain. To explore the origin and development of MNNC, we searched for neoplasia-associated mutational change in oncogene and tumor suppressor genes. Specifically, we analyzed KRAS oncogene mutations by polymerase chain reaction/dideoxy DNA (Sanger) sequencing and tumor suppression gene deletion by loss of heterozygosity (LOH) using polymerase chain reaction/capillary gel electrophoresis for a panel of 16 polymorphic microsatellite repeat markers targeting common tumor suppression gene loci at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, and 22q on DNA isolated from the cystic lining epithelium microdissected from 15 surgically diagnosed MNNCs by microdissection of unstained histologic sections of fixed resection specimens. DNA mutations were demonstrated in 4 of 15 cases: 1 with KRAS mutation at codon 12 glycine (G) substitution by aspartic acid (D) (G12D), 1 with KRAS mutation at 12 glycine (G) substitution by arginine (R) (G12R), 1 with LOH at 10q (PTEN), and 1 with LOH at 17q (RNF43). Therefore, although the genomic mutation rate detected in MNNC is relatively low, our results indicate that MNNCs may acquire genetic alteration similar to low-grade pancreatic intraepithelial neoplasia, furthering debate of the true nature of these lesions.
authors.affiliation: Department of Pathology of Northwestern Memorial Hospital, Northwestern University, Chicago, IL 60611.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Interpace Diagnostics, Pittsburgh, PA 15222.
authors.forename: Sydney D
authors.initials: SD
authors.lastname: Finkelstein
authors.affiliation: Department of Pathology of Northwestern Memorial Hospital, Northwestern University, Chicago, IL 60611.
authors.forename: Gong
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Medicine of Northwestern Memorial Hospital, Northwestern University, Chicago, IL 60611.
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Keswani
authors.affiliation: Department of Pathology of Northwestern Memorial Hospital, Northwestern University, Chicago, IL 60611. Electronic address: xlin@northwestern.edu.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Lin
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D019075:Electrophoresis, Capillary; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010181:Pancreatic Cyst / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; C117307:KRAS protein, human; D015513:Oncogene Proteins; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Histomorphology; KRAS; Loss of heterozygosity; MNNC; Molecular analysis