Sonia Garrigou1, Geraldine Perkins2, Fanny Garlan1, Corinne Normand1, Audrey Didelot1, Delphine Le Corre1, Sanam Peyvandi3, Claire Mulot4, Ralph Niarra5, Pascaline Aucouturier5, Gilles Chatellier5, Philippe Nizard1, Karla Perez-Toralla1, Eleonora Zonta1, Cecile Charpy3, Anais Pujals6, Caroline Barau7, Olivier Bouché8, Jean-François Emile9, Denis Pezet10, Frederic Bibeau11, J Brian Hutchison12, Darren R Link12, Aziz Zaanan2, Pierre Laurent-Puig13, Iradj Sobhani14, Valerie Taly15. 1. Université Paris Sorbonne Cité, INSERM UMR-S1147, CNRS SNC5014, Centre Universitaire des Saints-Pères, Paris Cedex 06, France. Equipe labélisée Ligue contre le cancer; 2. Université Paris Sorbonne Cité, INSERM UMR-S1147, CNRS SNC5014, Centre Universitaire des Saints-Pères, Paris Cedex 06, France. Equipe labélisée Ligue contre le cancer; Department of Digestive Oncology, AP-HP, European Georges Pompidou Hospital, Paris Descartes University, Paris, France; 3. Department of Gastroenterology, Henri-Mondor Hospital-APHP and EA 7375-EC2M3 Laboratory, University of Paris Est Creteil Val de Marne, Creteil, France; 4. Université Paris Sorbonne Cité, INSERM UMR-S1147, CNRS SNC5014, Centre Universitaire des Saints-Pères, Paris Cedex 06, France. Equipe labélisée Ligue contre le cancer; CRB Epigenetec, INSERM UMR-S1147, Centre Universitaire des Saints-Pères, Paris Cedex 06, France; 5. CIC-EC4 URC HEGP, AP-HP, Hôpitaux Universitaires Paris Ouest, Paris, France; 6. INSERM U955, University of Paris Est Creteil Val de Marne and Department of Pathology, AP-HP, Henri-Mondor Hospital, Créteil, France; 7. CRB, AP-HP, Henri-Mondor Hospital, Créteil, France; 8. Service d'hépatogastroentérologie et de cancérologie digestive, CHU de Reims, Hôpital Robert-Debré, Reims Cedex, France; 9. Department of Pathology, Hôpital Ambroise Paré, AP-HP, Université de Versailles St Quentin en Yvelines, Boulogne-Billancourt, France; 10. CHU Clermont Ferrand, Clermont Ferrand Cedex 1, France; 11. Service d'Anatomo-Pathologie, Centre Val d'Aurelle Paul-Lamarque, Montpellier, France; 12. RainDance Technologies, Billerica, MA; 13. Université Paris Sorbonne Cité, INSERM UMR-S1147, CNRS SNC5014, Centre Universitaire des Saints-Pères, Paris Cedex 06, France. Equipe labélisée Ligue contre le cancer; Department of Biology, European Georges Pompidou Hospital, AP-HP, Paris Descartes University, Paris, France. valerie.taly@parisdescartes.fr pierre.laurent-puig@parisdescartes.fr iradj.sobhani@hmn.aphp.fr. 14. Department of Gastroenterology, Henri-Mondor Hospital-APHP and EA 7375-EC2M3 Laboratory, University of Paris Est Creteil Val de Marne, Creteil, France; valerie.taly@parisdescartes.fr pierre.laurent-puig@parisdescartes.fr iradj.sobhani@hmn.aphp.fr. 15. Université Paris Sorbonne Cité, INSERM UMR-S1147, CNRS SNC5014, Centre Universitaire des Saints-Pères, Paris Cedex 06, France. Equipe labélisée Ligue contre le cancer; valerie.taly@parisdescartes.fr pierre.laurent-puig@parisdescartes.fr iradj.sobhani@hmn.aphp.fr.
Abstract
BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS: We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS: Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS: These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.
BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS: We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS: Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS: These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.
Authors: Manny D Bacolod; Aashiq H Mirza; Jianmin Huang; Sarah F Giardina; Philip B Feinberg; Steven A Soper; Francis Barany Journal: J Mol Diagn Date: 2020-05-12 Impact factor: 5.568
Authors: Andrea Sartore-Bianchi; Federica Di Nicolantonio; Ludovic Barault; Alessio Amatu; Giulia Siravegna; Agostino Ponzetti; Sebastian Moran; Andrea Cassingena; Benedetta Mussolin; Chiara Falcomatà; Alexandra M Binder; Carmen Cristiano; Daniele Oddo; Simonetta Guarrera; Carlotta Cancelliere; Sara Bustreo; Katia Bencardino; Sean Maden; Alice Vanzati; Patrizia Zavattari; Giuseppe Matullo; Mauro Truini; William M Grady; Patrizia Racca; Karin B Michels; Salvatore Siena; Manel Esteller; Alberto Bardelli Journal: Gut Date: 2017-10-05 Impact factor: 23.059