GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct
Hanno Matthaei
Departments of Pathology
Department of Surgery, University of Bonn, Bonn, Germany
These authors contributed equally to this work.
Search for more papers by this authorJian Wu
Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, China
These authors contributed equally to this work.
Search for more papers by this authorPhilipp Lingohr
Department of Surgery, University of Bonn, Bonn, Germany
Search for more papers by this authorNora Katabi
Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, USA
Search for more papers by this authorDavid S. Klimstra
Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, USA
Search for more papers by this authorN. Volkan Adsay
Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
Search for more papers by this authorRichard D. Schulick
Departments of Pathology
Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorKenneth W. Kinzler
Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorBert Vogelstein
Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Oncology, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorCorresponding Author
Anirban Maitra
Departments of Pathology
Oncology
Anirban Maitra, Departments of Pathology and Oncology, Sol Goldman Pancreatic Cancer Research Center, 1550 Orleans Street, CRB II, Room 345, Baltimore, MD 21231, USA. Tel: + 1 410 955 3511. Fax: + 1 410 614 0671. E-mail: [email protected]Search for more papers by this authorHanno Matthaei
Departments of Pathology
Department of Surgery, University of Bonn, Bonn, Germany
These authors contributed equally to this work.
Search for more papers by this authorJian Wu
Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, China
These authors contributed equally to this work.
Search for more papers by this authorPhilipp Lingohr
Department of Surgery, University of Bonn, Bonn, Germany
Search for more papers by this authorNora Katabi
Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, USA
Search for more papers by this authorDavid S. Klimstra
Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, USA
Search for more papers by this authorN. Volkan Adsay
Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
Search for more papers by this authorRichard D. Schulick
Departments of Pathology
Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorKenneth W. Kinzler
Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorBert Vogelstein
Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Oncology, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorCorresponding Author
Anirban Maitra
Departments of Pathology
Oncology
Anirban Maitra, Departments of Pathology and Oncology, Sol Goldman Pancreatic Cancer Research Center, 1550 Orleans Street, CRB II, Room 345, Baltimore, MD 21231, USA. Tel: + 1 410 955 3511. Fax: + 1 410 614 0671. E-mail: [email protected]Search for more papers by this authorAbstract
Background: Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs.
Methods: Thirty-four patients were included. DNA from microdissected IPNBs was subjected to a polymerase chain reaction and ligation method for the detection of GNAS mutations at codon 201 and of KRAS mutations at codon 12. Mutational status was compared with clinical and pathologic data.
Results: The IPNBs had a median diameter of 3.5 cm and were located intrahepatically (n= 6), extrahepatically (n= 13), both intra- and extrahepatically (n= 4) or in the gallbladder (intracystic papillary neoplasms, n= 11). Most exhibited pancreatobiliary differentiation (n= 20), high-grade dysplasia (n= 26) and an associated adenocarcinoma (n= 20). Analysis of GNAS codon 201 identified only one mutant sample in a multifocal intestinal subtype intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon 12 mutation.
Conclusions: GNAS codon 201 mutations are uncommon in IPNBs, by contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed to uncover the pathways involved in IPNB development.
Supporting Information
Table S1. Detailed clinical and histopathologic data for the study population.
Table S2. Oligonucleotides used for sensitive polymerase chain reaction ligation method for detecting GNAS and KRAS mutations.
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| HPB_504_sm_tS1-S2.doc134.5 KB | Supporting info item |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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