Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multi...

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Main Authors: Rémy Nicolle, Cindy Canivet, Laurent Palazzo, Bertrand Napoléon, Mira Ayadi, Camille Pignolet, Jérôme Cros, Sophie Gourgou, Janick Selves, Jérôme Torrisani, Nelson Dusetti, Pierre Cordelier, Louis Buscail, Barbara Bournet, Nicolas Carrère, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, Corinne Couteau, Marion Deslandres, Pascale Rivera, Emily Alouany, Nadim Fares, Karl Barange, Anne Gomez-Brouchet, Adrian Culetto, Guillaume Le Cosquer, Marion Jaffrelot, Bertrand Pujol, Fabien Fumex, Jérôme Desrame, Christine Lefort, Vincent Lepilliez, Rodica Gincul, Pascal Artru, Léa Clavel, Anne-Isabelle Lemaistre, Sarah Tubiana, Nicolas Flori, Pierre Senesse, Pierre-Emmanuel Colombo, Emmanuelle Samalin-Scalzi, Fabienne Portales, Lise Roca, Claire Honfo Ga, Carinne Plassot, Marc Ychou, Pierre Guibert, Christelle De La Fouchardière, Mathieu Sarabi, Patrice Peyrat, Séverine Tabone-Eglinger, Caroline Renard, Guillaume Piessen, Stéphanie Truant, Alain Saudemont, Guillaume Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gelé, Eric Assenat, Jean-Michel Fabre, François-Régis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, Jean-François Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella-Branger, Véronique Vendrely, Clément Subtil, Eric Terrebonne, Jean-Frédéric Blanc, Jean-Philippe Merlio, Dominique Farges-Bancel, Jean-Marc Gornet, Daniela Geromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie-Christine Saint-Paul, Philippe Berthélémy, Chelbabi Fouad, Stéphane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, Cyrille Delpierre
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Language:English
Published: Elsevier 2024-11-01
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396424004092
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author Rémy Nicolle
Cindy Canivet
Laurent Palazzo
Bertrand Napoléon
Mira Ayadi
Camille Pignolet
Jérôme Cros
Sophie Gourgou
Janick Selves
Jérôme Torrisani
Nelson Dusetti
Pierre Cordelier
Louis Buscail
Barbara Bournet
Barbara Bournet
Cindy Canivet
Louis Buscail
Nicolas Carrère
Fabrice Muscari
Bertrand Suc
Rosine Guimbaud
Corinne Couteau
Marion Deslandres
Pascale Rivera
Emily Alouany
Nadim Fares
Karl Barange
Janick Selves
Anne Gomez-Brouchet
Adrian Culetto
Guillaume Le Cosquer
Marion Jaffrelot
Bertrand Napoléon
Bertrand Pujol
Fabien Fumex
Jérôme Desrame
Christine Lefort
Vincent Lepilliez
Rodica Gincul
Pascal Artru
Léa Clavel
Anne-Isabelle Lemaistre
Laurent Palazzo
Jérôme Cros
Sarah Tubiana
Nicolas Flori
Pierre Senesse
Pierre-Emmanuel Colombo
Emmanuelle Samalin-Scalzi
Fabienne Portales
Sophie Gourgou
Lise Roca
Claire Honfo Ga
Carinne Plassot
Marc Ychou
Pierre Guibert
Christelle De La Fouchardière
Mathieu Sarabi
Patrice Peyrat
Séverine Tabone-Eglinger
Caroline Renard
Guillaume Piessen
Stéphanie Truant
Alain Saudemont
Guillaume Millet
Florence Renaud
Emmanuelle Leteurtre
Patrick Gelé
Eric Assenat
Jean-Michel Fabre
François-Régis Souche
Marie Dupuy
Anne-Marie Gorce-Dupuy
Jeanne Ramos
Jean-François Seitz
Jean Hardwigsen
Emmanuelle Norguet-Monnereau
Philippe Grandval
Muriel Duluc
Dominique Figarella-Branger
Véronique Vendrely
Clément Subtil
Eric Terrebonne
Jean-Frédéric Blanc
Jean-Philippe Merlio
Dominique Farges-Bancel
Jean-Marc Gornet
Daniela Geromin
Geoffroy Vanbiervliet
Anne-Claire Frin
Delphine Ouvrier
Marie-Christine Saint-Paul
Philippe Berthélémy
Chelbabi Fouad
Stéphane Garcia
Nathalie Lesavre
Mohamed Gasmi
Marc Barthet
Vanessa Cottet
Cyrille Delpierre
author_facet Rémy Nicolle
Cindy Canivet
Laurent Palazzo
Bertrand Napoléon
Mira Ayadi
Camille Pignolet
Jérôme Cros
Sophie Gourgou
Janick Selves
Jérôme Torrisani
Nelson Dusetti
Pierre Cordelier
Louis Buscail
Barbara Bournet
Barbara Bournet
Cindy Canivet
Louis Buscail
Nicolas Carrère
Fabrice Muscari
Bertrand Suc
Rosine Guimbaud
Corinne Couteau
Marion Deslandres
Pascale Rivera
Emily Alouany
Nadim Fares
Karl Barange
Janick Selves
Anne Gomez-Brouchet
Adrian Culetto
Guillaume Le Cosquer
Marion Jaffrelot
Bertrand Napoléon
Bertrand Pujol
Fabien Fumex
Jérôme Desrame
Christine Lefort
Vincent Lepilliez
Rodica Gincul
Pascal Artru
Léa Clavel
Anne-Isabelle Lemaistre
Laurent Palazzo
Jérôme Cros
Sarah Tubiana
Nicolas Flori
Pierre Senesse
Pierre-Emmanuel Colombo
Emmanuelle Samalin-Scalzi
Fabienne Portales
Sophie Gourgou
Lise Roca
Claire Honfo Ga
Carinne Plassot
Marc Ychou
Pierre Guibert
Christelle De La Fouchardière
Mathieu Sarabi
Patrice Peyrat
Séverine Tabone-Eglinger
Caroline Renard
Guillaume Piessen
Stéphanie Truant
Alain Saudemont
Guillaume Millet
Florence Renaud
Emmanuelle Leteurtre
Patrick Gelé
Eric Assenat
Jean-Michel Fabre
François-Régis Souche
Marie Dupuy
Anne-Marie Gorce-Dupuy
Jeanne Ramos
Jean-François Seitz
Jean Hardwigsen
Emmanuelle Norguet-Monnereau
Philippe Grandval
Muriel Duluc
Dominique Figarella-Branger
Véronique Vendrely
Clément Subtil
Eric Terrebonne
Jean-Frédéric Blanc
Jean-Philippe Merlio
Dominique Farges-Bancel
Jean-Marc Gornet
Daniela Geromin
Geoffroy Vanbiervliet
Anne-Claire Frin
Delphine Ouvrier
Marie-Christine Saint-Paul
Philippe Berthélémy
Chelbabi Fouad
Stéphane Garcia
Nathalie Lesavre
Mohamed Gasmi
Marc Barthet
Vanessa Cottet
Cyrille Delpierre
author_sort Rémy Nicolle
collection DOAJ
description Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).
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spelling doaj-art-42b1e90f321d4eb681ad93fd73b2d3f52025-08-20T02:14:42ZengElsevierEBioMedicine2352-39642024-11-0110910537310.1016/j.ebiom.2024.105373Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in contextRémy Nicolle0Cindy Canivet1Laurent Palazzo2Bertrand Napoléon3Mira Ayadi4Camille Pignolet5Jérôme Cros6Sophie Gourgou7Janick Selves8Jérôme Torrisani9Nelson Dusetti10Pierre Cordelier11Louis Buscail12Barbara Bournet13Barbara BournetCindy CanivetLouis BuscailNicolas CarrèreFabrice MuscariBertrand SucRosine GuimbaudCorinne CouteauMarion DeslandresPascale RiveraEmily AlouanyNadim FaresKarl BarangeJanick SelvesAnne Gomez-BrouchetAdrian CulettoGuillaume Le CosquerMarion JaffrelotBertrand NapoléonBertrand PujolFabien FumexJérôme DesrameChristine LefortVincent LepilliezRodica GinculPascal ArtruLéa ClavelAnne-Isabelle LemaistreLaurent PalazzoJérôme CrosSarah TubianaNicolas FloriPierre SenessePierre-Emmanuel ColomboEmmanuelle Samalin-ScalziFabienne PortalesSophie GourgouLise RocaClaire Honfo GaCarinne PlassotMarc YchouPierre GuibertChristelle De La FouchardièreMathieu SarabiPatrice PeyratSéverine Tabone-EglingerCaroline RenardGuillaume PiessenStéphanie TruantAlain SaudemontGuillaume MilletFlorence RenaudEmmanuelle LeteurtrePatrick GeléEric AssenatJean-Michel FabreFrançois-Régis SoucheMarie DupuyAnne-Marie Gorce-DupuyJeanne RamosJean-François SeitzJean HardwigsenEmmanuelle Norguet-MonnereauPhilippe GrandvalMuriel DulucDominique Figarella-BrangerVéronique VendrelyClément SubtilEric TerrebonneJean-Frédéric BlancJean-Philippe MerlioDominique Farges-BancelJean-Marc GornetDaniela GerominGeoffroy VanbiervlietAnne-Claire FrinDelphine OuvrierMarie-Christine Saint-PaulPhilippe BerthélémyChelbabi FouadStéphane GarciaNathalie LesavreMohamed GasmiMarc BarthetVanessa CottetCyrille DelpierreUniversité Paris Cité, Centre de Recherche sur l’Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, FranceService de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, FranceService d’Endoscopie, Clinique du Trocadéro, Paris, FranceService de Gastroentérologie, Hôpital Privé Jean Mermoz, Ramsay Générale de Santé, Lyon, FranceProgramme Cartes d’Identité des Tumeurs, Ligue Nationale Contre Le Cancer, Paris, FranceUniversité Paris Cité, Centre de Recherche sur l’Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, FranceUniversité Paris Cité, Centre de Recherche sur l’Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, France; Université Paris Cité, Service d’Anatomopathologie, Centre Hospitalier Universitaire Beaujon/Bichat (APHP), Clichy/Paris, FranceInstitut du Cancer de Montpellier-Val d’Aurelle, Université de Montpellier, Montpellier, FranceService d’Anatomopathologie, Institut Universitaire du Cancer-Oncopole de Toulouse, Centre Hospitalier Universitaire (CHU), Toulouse, FranceCentre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, FranceCentre de Recherche sur le Cancer de Marseille, Inserm, CNRS, Institut Paoli-Calmettes, Université Aix-Marseille, Marseille, FranceCentre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, FranceService de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, France; Centre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, France; Corresponding author. Service de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse cedex 9, France.Service de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, France; Centre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, FranceSummary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).http://www.sciencedirect.com/science/article/pii/S2352396424004092Pancreatic cancerRNA sequencingTargeted DNA deep sequencingTranslational medicinePredictive medicine
spellingShingle Rémy Nicolle
Cindy Canivet
Laurent Palazzo
Bertrand Napoléon
Mira Ayadi
Camille Pignolet
Jérôme Cros
Sophie Gourgou
Janick Selves
Jérôme Torrisani
Nelson Dusetti
Pierre Cordelier
Louis Buscail
Barbara Bournet
Barbara Bournet
Cindy Canivet
Louis Buscail
Nicolas Carrère
Fabrice Muscari
Bertrand Suc
Rosine Guimbaud
Corinne Couteau
Marion Deslandres
Pascale Rivera
Emily Alouany
Nadim Fares
Karl Barange
Janick Selves
Anne Gomez-Brouchet
Adrian Culetto
Guillaume Le Cosquer
Marion Jaffrelot
Bertrand Napoléon
Bertrand Pujol
Fabien Fumex
Jérôme Desrame
Christine Lefort
Vincent Lepilliez
Rodica Gincul
Pascal Artru
Léa Clavel
Anne-Isabelle Lemaistre
Laurent Palazzo
Jérôme Cros
Sarah Tubiana
Nicolas Flori
Pierre Senesse
Pierre-Emmanuel Colombo
Emmanuelle Samalin-Scalzi
Fabienne Portales
Sophie Gourgou
Lise Roca
Claire Honfo Ga
Carinne Plassot
Marc Ychou
Pierre Guibert
Christelle De La Fouchardière
Mathieu Sarabi
Patrice Peyrat
Séverine Tabone-Eglinger
Caroline Renard
Guillaume Piessen
Stéphanie Truant
Alain Saudemont
Guillaume Millet
Florence Renaud
Emmanuelle Leteurtre
Patrick Gelé
Eric Assenat
Jean-Michel Fabre
François-Régis Souche
Marie Dupuy
Anne-Marie Gorce-Dupuy
Jeanne Ramos
Jean-François Seitz
Jean Hardwigsen
Emmanuelle Norguet-Monnereau
Philippe Grandval
Muriel Duluc
Dominique Figarella-Branger
Véronique Vendrely
Clément Subtil
Eric Terrebonne
Jean-Frédéric Blanc
Jean-Philippe Merlio
Dominique Farges-Bancel
Jean-Marc Gornet
Daniela Geromin
Geoffroy Vanbiervliet
Anne-Claire Frin
Delphine Ouvrier
Marie-Christine Saint-Paul
Philippe Berthélémy
Chelbabi Fouad
Stéphane Garcia
Nathalie Lesavre
Mohamed Gasmi
Marc Barthet
Vanessa Cottet
Cyrille Delpierre
Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context
EBioMedicine
Pancreatic cancer
RNA sequencing
Targeted DNA deep sequencing
Translational medicine
Predictive medicine
title Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context
title_full Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context
title_fullStr Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context
title_full_unstemmed Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context
title_short Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context
title_sort predictive genomic and transcriptomic analysis on endoscopic ultrasound guided fine needle aspiration materials from primary pancreatic adenocarcinoma a prospective multicentre studyresearch in context
topic Pancreatic cancer
RNA sequencing
Targeted DNA deep sequencing
Translational medicine
Predictive medicine
url http://www.sciencedirect.com/science/article/pii/S2352396424004092
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