Molecular genetics of pancreatic intraepithelial neoplasia

被引:199
|
作者
Feldmann, Georg
Beaty, Robert
Hruban, Ralph H.
Maitra, Anirban
机构
[1] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Oncol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA
来源
JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY | 2007年 / 14卷 / 03期
关键词
D O I
10.1007/s00534-006-1166-5
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background. Recent evidence suggests that noninvasive precursor lesions, classified as pancreatic intraepithelial neoplasia (PanIN), can progress to invasive pancreatic cancer. This review will discuss the major genetic alterations in PanIN lesions. Methods. A comprehensive review of the literature was performed in order to find studies on the molecular profile of human PanIN lesions. In addition, recent publications on genetically engineered mouse models of preinvasive neoplasia and pancreatic cancers were reviewed. Results. PanINs demonstrate abnormalities at the genomic ( DNA), transcriptomic ( RNA), and proteomic levels, and there is a progressive accumulation of molecular alterations that accompany the histological progression from low-grade PanIN-1A to high-grade PanIN-3 lesions. Molecular changes in PanINs can be classified as "early" (KRAS2 mutations, telomere shortening, p21(WAF1/CIP1) up-regulation, etc.), "intermediate" ( cyclin D1 up-regulation, expression of proliferation antigens, etc.), or " late" (BRCA2 and TP53 mutations, DPC4/ SMAD4/MADH4 inactivation, etc.). All the genetic changes observed in PanINs are also found in invasive ductal adenocarcinomas, where they usually occur at a higher frequency. Genetically engineered mice expressing mutant Kras in the pancreas, with or without additional genetic alterations, provide a unique in vivo platform to study the pancreatic cancer progression model. Conclusions. Molecular studies have been instrumental in establishing that PanIN lesions are the noninvasive precursors for invasive ductal adenocarcinomas. The availability of molecular date provides the basis for designing rational early detection strategies and therapeutic intervention trials before pancreatic neoplasms invade, with the intention of alleviating the dismal prognosis associated with this disease.
引用
收藏
页码:224 / 232
页数:9
相关论文
共 50 条
  • [21] Molecular Biomarkers of Pancreatic Intraepithelial Neoplasia and Their Implications in Early Diagnosis and Therapeutic Intervention of Pancreatic Cancer
    Guo, Junli
    Xie, Keping
    Zheng, Shaojiang
    INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2016, 12 (03): : 292 - 301
  • [22] Survivin expression in pancreatic intraepithelial neoplasia (PanIN)
    Bhanot, U. K.
    Moller, P.
    Hasel, C.
    JOURNAL OF PATHOLOGY, 2006, 210 : 20 - 20
  • [23] Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia
    Ma, Changqing
    Gocke, Christopher D.
    Hruban, Ralph H.
    Belchis, Deborah A.
    HUMAN PATHOLOGY, 2016, 48 : 117 - 121
  • [24] Incidence of Pancreatic Intraepithelial Neoplasia in an Autopsy Series
    Longnecker, Daniel S.
    Suriawinata, Arief A.
    PANCREAS, 2022, 51 (04) : 305 - 309
  • [25] Quantitative proteomics investigation of pancreatic intraepithelial neoplasia
    Pan, Sheng
    Chen, Ru
    Reimel, Beth Ann
    Crispin, David A.
    Mirzaei, Hamid
    Cooke, Kelly
    Coleman, Joshua F.
    Lane, Zhaoli
    Bronner, Mary P.
    Goodlett, David R.
    McIntosh, Martin W.
    Traverso, William
    Aebersold, Ruedi
    Brentnall, Teresa A.
    ELECTROPHORESIS, 2009, 30 (07) : 1132 - 1144
  • [26] Pancreatic ductal adenocarcinoma associated with pancreatic ductal intraepithelial neoplasia
    Umesh K Bhanot
    Hepatobiliary&PancreaticDiseasesInternational, 2008, (01) : 106 - 107
  • [27] Expression of urocortin in pancreatic ductal adenocarcinoma and pancreatic intraepithelial neoplasia
    Cheng, Ming-Fang
    Tsai, Wen-Chiuan
    Hsia, Kan-Tai
    Yang, Ya-Sung
    Jin, Jong-Shiaw
    APMIS, 2014, 122 (02) : 147 - 154
  • [28] In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging
    Eser, Stefan
    Messer, Marlena
    Eser, Philipp
    von Werder, Alexander
    Seidler, Barbara
    Bajbouj, Monther
    Vogelmann, Roger
    Meining, Alexander
    von Burstin, Johannes
    Alguel, Hana
    Pagel, Philipp
    Schnieke, Angelika E.
    Esposito, Irene
    Schmid, Roland M.
    Schneider, Guenter
    Saur, Dieter
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (24) : 9945 - 9950
  • [29] Prevalence of pancreatic intraepithelial neoplasia (PanIN) in association with pancreatic adenocarcinoma
    Davis, WG
    Laszik, ZG
    LABORATORY INVESTIGATION, 2003, 83 (01) : 272A - 272A
  • [30] Prevalence of pancreatic intraepithelial neoplasia (PanIN) in association with pancreatic adenocarcinoma
    Davis, WG
    Laszik, ZG
    MODERN PATHOLOGY, 2003, 16 (01) : 272A - 272A