KRAS/GNAS‐testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound‐guided workup of suspected mucinous neoplasms of the pancreas
Pancreatic cysts or dilated pancreatic ducts are often found by cross‐sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non‐mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted ne...
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| Veröffentlicht in: | Genes chromosomes & cancer 2021-07, Vol.60 (7), p.489-497 |
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| creator | Schmitz, Daniel Kazdal, Daniel Allgäuer, Michael Trunk, Marcus Vornhusen, Sylke Nahm, Anna‐Maria Doll, Matthias Weingärtner, Simon Endris, Volker Penzel, Roland Kirchner, Martina Brandt, Regine Neumann, Olaf Sültmann, Holger Budczies, Jan Kienle, Peter Magdeburg, Richard Hetjens, Svetlana Schirmacher, Peter Bergmann, Frank Rudi, Jochen Stenzinger, Albrecht Volckmar, Anna‐Lena |
| description | Pancreatic cysts or dilated pancreatic ducts are often found by cross‐sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non‐mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell‐free DNA in the diagnostic endoscopic ultrasound (EUS)‐guided workup. Pancreatic cyst(s) or main duct fluid obtained by EUS‐guided FNA was analysed by carcinoembryonic antigen (CEA), cytology and deep targeted NGS of 14 known gastrointestinal cancer genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) with a limit of detection down to variant allele frequency of 0.01%. Results were correlated to histopathology and clinical follow‐up. One hundred and thirteen patients with pancreatic cyst(s) and/or a dilated pancreatic main duct (≥5 mm) were screened. Sixty‐six patients had to be excluded, mainly due to inoperability or small cyst size (≤10 mm). Forty‐seven patients were enrolled for further analysis. A final diagnosis was available in 27 cases including 8 negative controls. In 43/47 (91.5%) of patients a KRAS‐ and/or GNAS‐mutation was diagnosed by NGS. 27.0% of the KRAS‐mutated and 10.0% of the GNAS‐mutated lesions harbored multiple mutations. KRAS/GNAS‐testing by NGS, cytology, and CEA had a sensitivity and specificity of 94.7/100%, 38.1/100%, and 42.1/75.0%, respectively. KRAS/GNAS‐testing was significantly superior to CEA (P = .0209) and cytology (P = .0016). In conclusion, KRAS/GNAS‐testing by deep targeted NGS is a suitable method to distinguish mucinous from non‐mucinous pancreatic lesions, suggesting its usage as a single diagnostic test. Results must be confirmed in a larger cohort. |
| doi_str_mv | 10.1002/gcc.22946 |
| format | Article |
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Therefore, distinction between mucinous and non‐mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell‐free DNA in the diagnostic endoscopic ultrasound (EUS)‐guided workup. Pancreatic cyst(s) or main duct fluid obtained by EUS‐guided FNA was analysed by carcinoembryonic antigen (CEA), cytology and deep targeted NGS of 14 known gastrointestinal cancer genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) with a limit of detection down to variant allele frequency of 0.01%. Results were correlated to histopathology and clinical follow‐up. One hundred and thirteen patients with pancreatic cyst(s) and/or a dilated pancreatic main duct (≥5 mm) were screened. Sixty‐six patients had to be excluded, mainly due to inoperability or small cyst size (≤10 mm). Forty‐seven patients were enrolled for further analysis. A final diagnosis was available in 27 cases including 8 negative controls. In 43/47 (91.5%) of patients a KRAS‐ and/or GNAS‐mutation was diagnosed by NGS. 27.0% of the KRAS‐mutated and 10.0% of the GNAS‐mutated lesions harbored multiple mutations. KRAS/GNAS‐testing by NGS, cytology, and CEA had a sensitivity and specificity of 94.7/100%, 38.1/100%, and 42.1/75.0%, respectively. KRAS/GNAS‐testing was significantly superior to CEA (P = .0209) and cytology (P = .0016). In conclusion, KRAS/GNAS‐testing by deep targeted NGS is a suitable method to distinguish mucinous from non‐mucinous pancreatic lesions, suggesting its usage as a single diagnostic test. Results must be confirmed in a larger cohort.</description><identifier>ISSN: 1045-2257</identifier><identifier>EISSN: 1098-2264</identifier><identifier>DOI: 10.1002/gcc.22946</identifier><identifier>PMID: 33686791</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adenomatous polyposis coli ; Aged ; Aged, 80 and over ; AKT1 protein ; Antigen-presenting cells ; Carcinoembryonic antigen ; Cdc4 protein ; Cellular biology ; Chromogranins - genetics ; Cysts ; Cytology ; DNA sequencing ; Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods ; Endoscopic Ultrasound-Guided Fine Needle Aspiration - standards ; endoscopic ultrasound‐guided fine needle aspiration ; Endoscopy ; Epidermal growth factor receptors ; ErbB-2 protein ; Female ; Gene frequency ; Genetic Testing - methods ; Genetic Testing - standards ; GTP-Binding Protein alpha Subunits, Gs - genetics ; High-Throughput Nucleotide Sequencing - methods ; High-Throughput Nucleotide Sequencing - standards ; high‐throughput nucleotide sequencing ; Humans ; intraductal papillary mucinous neoplasms of the pancreas ; K-Ras protein ; Lesions ; Male ; Middle Aged ; Mutation ; Neoplasms, Cystic, Mucinous, and Serous - diagnostic imaging ; Neoplasms, Cystic, Mucinous, and Serous - genetics ; Neoplasms, Cystic, Mucinous, and Serous - pathology ; Next-generation sequencing ; p53 Protein ; Pancreas ; Pancreatic cancer ; Pancreatic Cyst - diagnostic imaging ; Pancreatic Cyst - genetics ; Pancreatic Cyst - pathology ; Pancreatic Neoplasms - diagnostic imaging ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Proto-Oncogene Proteins p21(ras) - genetics ; Sensitivity analysis ; Sensitivity and Specificity ; Sequence Analysis, DNA - methods ; Sequence Analysis, DNA - standards ; Smad4 protein ; Ultrasonic imaging ; Ultrasound</subject><ispartof>Genes chromosomes & cancer, 2021-07, Vol.60 (7), p.489-497</ispartof><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4196-71b23dc6aac2c6e7c47899f3fc30cdc6495e548a9287ff5042da8aba0ad3c9dd3</citedby><cites>FETCH-LOGICAL-c4196-71b23dc6aac2c6e7c47899f3fc30cdc6495e548a9287ff5042da8aba0ad3c9dd3</cites><orcidid>0000-0002-3273-8435</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fgcc.22946$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fgcc.22946$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33686791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmitz, Daniel</creatorcontrib><creatorcontrib>Kazdal, Daniel</creatorcontrib><creatorcontrib>Allgäuer, Michael</creatorcontrib><creatorcontrib>Trunk, Marcus</creatorcontrib><creatorcontrib>Vornhusen, Sylke</creatorcontrib><creatorcontrib>Nahm, Anna‐Maria</creatorcontrib><creatorcontrib>Doll, Matthias</creatorcontrib><creatorcontrib>Weingärtner, Simon</creatorcontrib><creatorcontrib>Endris, Volker</creatorcontrib><creatorcontrib>Penzel, Roland</creatorcontrib><creatorcontrib>Kirchner, Martina</creatorcontrib><creatorcontrib>Brandt, Regine</creatorcontrib><creatorcontrib>Neumann, Olaf</creatorcontrib><creatorcontrib>Sültmann, Holger</creatorcontrib><creatorcontrib>Budczies, Jan</creatorcontrib><creatorcontrib>Kienle, Peter</creatorcontrib><creatorcontrib>Magdeburg, Richard</creatorcontrib><creatorcontrib>Hetjens, Svetlana</creatorcontrib><creatorcontrib>Schirmacher, Peter</creatorcontrib><creatorcontrib>Bergmann, Frank</creatorcontrib><creatorcontrib>Rudi, Jochen</creatorcontrib><creatorcontrib>Stenzinger, Albrecht</creatorcontrib><creatorcontrib>Volckmar, Anna‐Lena</creatorcontrib><title>KRAS/GNAS‐testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound‐guided workup of suspected mucinous neoplasms of the pancreas</title><title>Genes chromosomes & cancer</title><addtitle>Genes Chromosomes Cancer</addtitle><description>Pancreatic cysts or dilated pancreatic ducts are often found by cross‐sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non‐mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell‐free DNA in the diagnostic endoscopic ultrasound (EUS)‐guided workup. Pancreatic cyst(s) or main duct fluid obtained by EUS‐guided FNA was analysed by carcinoembryonic antigen (CEA), cytology and deep targeted NGS of 14 known gastrointestinal cancer genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) with a limit of detection down to variant allele frequency of 0.01%. Results were correlated to histopathology and clinical follow‐up. One hundred and thirteen patients with pancreatic cyst(s) and/or a dilated pancreatic main duct (≥5 mm) were screened. Sixty‐six patients had to be excluded, mainly due to inoperability or small cyst size (≤10 mm). Forty‐seven patients were enrolled for further analysis. A final diagnosis was available in 27 cases including 8 negative controls. In 43/47 (91.5%) of patients a KRAS‐ and/or GNAS‐mutation was diagnosed by NGS. 27.0% of the KRAS‐mutated and 10.0% of the GNAS‐mutated lesions harbored multiple mutations. KRAS/GNAS‐testing by NGS, cytology, and CEA had a sensitivity and specificity of 94.7/100%, 38.1/100%, and 42.1/75.0%, respectively. KRAS/GNAS‐testing was significantly superior to CEA (P = .0209) and cytology (P = .0016). In conclusion, KRAS/GNAS‐testing by deep targeted NGS is a suitable method to distinguish mucinous from non‐mucinous pancreatic lesions, suggesting its usage as a single diagnostic test. Results must be confirmed in a larger cohort.</description><subject>Adenomatous polyposis coli</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT1 protein</subject><subject>Antigen-presenting cells</subject><subject>Carcinoembryonic antigen</subject><subject>Cdc4 protein</subject><subject>Cellular biology</subject><subject>Chromogranins - genetics</subject><subject>Cysts</subject><subject>Cytology</subject><subject>DNA sequencing</subject><subject>Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods</subject><subject>Endoscopic Ultrasound-Guided Fine Needle Aspiration - standards</subject><subject>endoscopic ultrasound‐guided fine needle aspiration</subject><subject>Endoscopy</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Gene frequency</subject><subject>Genetic Testing - methods</subject><subject>Genetic Testing - standards</subject><subject>GTP-Binding Protein alpha Subunits, Gs - genetics</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>High-Throughput Nucleotide Sequencing - standards</subject><subject>high‐throughput nucleotide sequencing</subject><subject>Humans</subject><subject>intraductal papillary mucinous neoplasms of the pancreas</subject><subject>K-Ras protein</subject><subject>Lesions</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasms, Cystic, Mucinous, and Serous - diagnostic imaging</subject><subject>Neoplasms, Cystic, Mucinous, and Serous - genetics</subject><subject>Neoplasms, Cystic, Mucinous, and Serous - pathology</subject><subject>Next-generation sequencing</subject><subject>p53 Protein</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Cyst - diagnostic imaging</subject><subject>Pancreatic Cyst - genetics</subject><subject>Pancreatic Cyst - pathology</subject><subject>Pancreatic Neoplasms - diagnostic imaging</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Sensitivity analysis</subject><subject>Sensitivity and Specificity</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Sequence Analysis, DNA - standards</subject><subject>Smad4 protein</subject><subject>Ultrasonic imaging</subject><subject>Ultrasound</subject><issn>1045-2257</issn><issn>1098-2264</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQhyNERUvhwAsgS1zgsF3HcRz7uFqVpaIqEoVz5LUnWZfEDv7TsjcegXfhjXiSOmzhgMTJI_vzNzP6FcWLEp-VGJNlr9QZIYKyR8VJiQVfEMLo47mmda7r5rh4GsINxphVon5SHFcV46wR5Unx8_3H1fVyc7W6_vX9R4QQje3Rdo92pt8NexTABhPNLSANMKEofQ8RNLLwLaIeLHgZjbOZ-5rAqvmzGSfvbiGguAMEVrug3GQUSkP0Mrhkde7UJ6Oz5s75L2lCrkMhhQnUrB5T1rgUcg83DTKMYX6fZZO0yoMMz4qjTg4Bnj-cp8Xnt-ef1u8Wlx82F-vV5ULRUrBFU25JpRWTUhHFoFG04UJ0VacqrPI9FTXUlEtBeNN1NaZESy63EktdKaF1dVq8PnjzQnm9ENvRBAXDIPNoKbSEClFxShuS0Vf_oDcueZuna0lNasY5ZzP15kAp70Lw0LWTN6P0-7bE7Zxkm5NsfyeZ2ZcPxrQdQf8l_0SXgeUBuDMD7P9vajfr9UF5DxDzrqI</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Schmitz, Daniel</creator><creator>Kazdal, Daniel</creator><creator>Allgäuer, Michael</creator><creator>Trunk, Marcus</creator><creator>Vornhusen, Sylke</creator><creator>Nahm, Anna‐Maria</creator><creator>Doll, Matthias</creator><creator>Weingärtner, Simon</creator><creator>Endris, Volker</creator><creator>Penzel, Roland</creator><creator>Kirchner, Martina</creator><creator>Brandt, Regine</creator><creator>Neumann, Olaf</creator><creator>Sültmann, Holger</creator><creator>Budczies, Jan</creator><creator>Kienle, Peter</creator><creator>Magdeburg, Richard</creator><creator>Hetjens, Svetlana</creator><creator>Schirmacher, Peter</creator><creator>Bergmann, Frank</creator><creator>Rudi, Jochen</creator><creator>Stenzinger, Albrecht</creator><creator>Volckmar, Anna‐Lena</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3273-8435</orcidid></search><sort><creationdate>202107</creationdate><title>KRAS/GNAS‐testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound‐guided workup of suspected mucinous neoplasms of the pancreas</title><author>Schmitz, Daniel ; Kazdal, Daniel ; Allgäuer, Michael ; Trunk, Marcus ; Vornhusen, Sylke ; Nahm, Anna‐Maria ; Doll, Matthias ; Weingärtner, Simon ; Endris, Volker ; Penzel, Roland ; Kirchner, Martina ; Brandt, Regine ; Neumann, Olaf ; Sültmann, Holger ; Budczies, Jan ; Kienle, Peter ; Magdeburg, Richard ; Hetjens, Svetlana ; Schirmacher, Peter ; Bergmann, Frank ; Rudi, Jochen ; Stenzinger, Albrecht ; Volckmar, Anna‐Lena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4196-71b23dc6aac2c6e7c47899f3fc30cdc6495e548a9287ff5042da8aba0ad3c9dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenomatous polyposis coli</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>AKT1 protein</topic><topic>Antigen-presenting cells</topic><topic>Carcinoembryonic antigen</topic><topic>Cdc4 protein</topic><topic>Cellular biology</topic><topic>Chromogranins - genetics</topic><topic>Cysts</topic><topic>Cytology</topic><topic>DNA sequencing</topic><topic>Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods</topic><topic>Endoscopic Ultrasound-Guided Fine Needle Aspiration - standards</topic><topic>endoscopic ultrasound‐guided fine needle aspiration</topic><topic>Endoscopy</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB-2 protein</topic><topic>Female</topic><topic>Gene frequency</topic><topic>Genetic Testing - methods</topic><topic>Genetic Testing - standards</topic><topic>GTP-Binding Protein alpha Subunits, Gs - genetics</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>High-Throughput Nucleotide Sequencing - standards</topic><topic>high‐throughput nucleotide sequencing</topic><topic>Humans</topic><topic>intraductal papillary mucinous neoplasms of the pancreas</topic><topic>K-Ras protein</topic><topic>Lesions</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasms, Cystic, Mucinous, and Serous - diagnostic imaging</topic><topic>Neoplasms, Cystic, Mucinous, and Serous - genetics</topic><topic>Neoplasms, Cystic, Mucinous, and Serous - pathology</topic><topic>Next-generation sequencing</topic><topic>p53 Protein</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Cyst - diagnostic imaging</topic><topic>Pancreatic Cyst - genetics</topic><topic>Pancreatic Cyst - pathology</topic><topic>Pancreatic Neoplasms - diagnostic imaging</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Sensitivity analysis</topic><topic>Sensitivity and Specificity</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Sequence Analysis, DNA - standards</topic><topic>Smad4 protein</topic><topic>Ultrasonic imaging</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmitz, Daniel</creatorcontrib><creatorcontrib>Kazdal, Daniel</creatorcontrib><creatorcontrib>Allgäuer, Michael</creatorcontrib><creatorcontrib>Trunk, Marcus</creatorcontrib><creatorcontrib>Vornhusen, Sylke</creatorcontrib><creatorcontrib>Nahm, Anna‐Maria</creatorcontrib><creatorcontrib>Doll, Matthias</creatorcontrib><creatorcontrib>Weingärtner, Simon</creatorcontrib><creatorcontrib>Endris, Volker</creatorcontrib><creatorcontrib>Penzel, Roland</creatorcontrib><creatorcontrib>Kirchner, Martina</creatorcontrib><creatorcontrib>Brandt, Regine</creatorcontrib><creatorcontrib>Neumann, Olaf</creatorcontrib><creatorcontrib>Sültmann, Holger</creatorcontrib><creatorcontrib>Budczies, Jan</creatorcontrib><creatorcontrib>Kienle, Peter</creatorcontrib><creatorcontrib>Magdeburg, Richard</creatorcontrib><creatorcontrib>Hetjens, Svetlana</creatorcontrib><creatorcontrib>Schirmacher, Peter</creatorcontrib><creatorcontrib>Bergmann, Frank</creatorcontrib><creatorcontrib>Rudi, Jochen</creatorcontrib><creatorcontrib>Stenzinger, Albrecht</creatorcontrib><creatorcontrib>Volckmar, Anna‐Lena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes chromosomes & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmitz, Daniel</au><au>Kazdal, Daniel</au><au>Allgäuer, Michael</au><au>Trunk, Marcus</au><au>Vornhusen, Sylke</au><au>Nahm, Anna‐Maria</au><au>Doll, Matthias</au><au>Weingärtner, Simon</au><au>Endris, Volker</au><au>Penzel, Roland</au><au>Kirchner, Martina</au><au>Brandt, Regine</au><au>Neumann, Olaf</au><au>Sültmann, Holger</au><au>Budczies, Jan</au><au>Kienle, Peter</au><au>Magdeburg, Richard</au><au>Hetjens, Svetlana</au><au>Schirmacher, Peter</au><au>Bergmann, Frank</au><au>Rudi, Jochen</au><au>Stenzinger, Albrecht</au><au>Volckmar, Anna‐Lena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>KRAS/GNAS‐testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound‐guided workup of suspected mucinous neoplasms of the pancreas</atitle><jtitle>Genes chromosomes & cancer</jtitle><addtitle>Genes Chromosomes Cancer</addtitle><date>2021-07</date><risdate>2021</risdate><volume>60</volume><issue>7</issue><spage>489</spage><epage>497</epage><pages>489-497</pages><issn>1045-2257</issn><eissn>1098-2264</eissn><abstract>Pancreatic cysts or dilated pancreatic ducts are often found by cross‐sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non‐mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell‐free DNA in the diagnostic endoscopic ultrasound (EUS)‐guided workup. Pancreatic cyst(s) or main duct fluid obtained by EUS‐guided FNA was analysed by carcinoembryonic antigen (CEA), cytology and deep targeted NGS of 14 known gastrointestinal cancer genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) with a limit of detection down to variant allele frequency of 0.01%. Results were correlated to histopathology and clinical follow‐up. One hundred and thirteen patients with pancreatic cyst(s) and/or a dilated pancreatic main duct (≥5 mm) were screened. Sixty‐six patients had to be excluded, mainly due to inoperability or small cyst size (≤10 mm). Forty‐seven patients were enrolled for further analysis. A final diagnosis was available in 27 cases including 8 negative controls. In 43/47 (91.5%) of patients a KRAS‐ and/or GNAS‐mutation was diagnosed by NGS. 27.0% of the KRAS‐mutated and 10.0% of the GNAS‐mutated lesions harbored multiple mutations. KRAS/GNAS‐testing by NGS, cytology, and CEA had a sensitivity and specificity of 94.7/100%, 38.1/100%, and 42.1/75.0%, respectively. KRAS/GNAS‐testing was significantly superior to CEA (P = .0209) and cytology (P = .0016). In conclusion, KRAS/GNAS‐testing by deep targeted NGS is a suitable method to distinguish mucinous from non‐mucinous pancreatic lesions, suggesting its usage as a single diagnostic test. Results must be confirmed in a larger cohort.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>33686791</pmid><doi>10.1002/gcc.22946</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3273-8435</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1045-2257 |
| ispartof | Genes chromosomes & cancer, 2021-07, Vol.60 (7), p.489-497 |
| issn | 1045-2257 1098-2264 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2499384472 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adenomatous polyposis coli Aged Aged, 80 and over AKT1 protein Antigen-presenting cells Carcinoembryonic antigen Cdc4 protein Cellular biology Chromogranins - genetics Cysts Cytology DNA sequencing Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods Endoscopic Ultrasound-Guided Fine Needle Aspiration - standards endoscopic ultrasound‐guided fine needle aspiration Endoscopy Epidermal growth factor receptors ErbB-2 protein Female Gene frequency Genetic Testing - methods Genetic Testing - standards GTP-Binding Protein alpha Subunits, Gs - genetics High-Throughput Nucleotide Sequencing - methods High-Throughput Nucleotide Sequencing - standards high‐throughput nucleotide sequencing Humans intraductal papillary mucinous neoplasms of the pancreas K-Ras protein Lesions Male Middle Aged Mutation Neoplasms, Cystic, Mucinous, and Serous - diagnostic imaging Neoplasms, Cystic, Mucinous, and Serous - genetics Neoplasms, Cystic, Mucinous, and Serous - pathology Next-generation sequencing p53 Protein Pancreas Pancreatic cancer Pancreatic Cyst - diagnostic imaging Pancreatic Cyst - genetics Pancreatic Cyst - pathology Pancreatic Neoplasms - diagnostic imaging Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Proto-Oncogene Proteins p21(ras) - genetics Sensitivity analysis Sensitivity and Specificity Sequence Analysis, DNA - methods Sequence Analysis, DNA - standards Smad4 protein Ultrasonic imaging Ultrasound |
| title | KRAS/GNAS‐testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound‐guided workup of suspected mucinous neoplasms of the pancreas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T16%3A35%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=KRAS/GNAS%E2%80%90testing%20by%20highly%20sensitive%20deep%20targeted%20next%20generation%20sequencing%20improves%20the%20endoscopic%20ultrasound%E2%80%90guided%20workup%20of%20suspected%20mucinous%20neoplasms%20of%20the%20pancreas&rft.jtitle=Genes%20chromosomes%20&%20cancer&rft.au=Schmitz,%20Daniel&rft.date=2021-07&rft.volume=60&rft.issue=7&rft.spage=489&rft.epage=497&rft.pages=489-497&rft.issn=1045-2257&rft.eissn=1098-2264&rft_id=info:doi/10.1002/gcc.22946&rft_dat=%3Cproquest_cross%3E2499384472%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2525688862&rft_id=info:pmid/33686791&rfr_iscdi=true |