A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker
Sonia Garrigou
(1)
,
Géraldine Perkins
(1, 2)
,
Fanny Garlan
(1)
,
Corinne Normand
(1)
,
Audrey Didelot
(1)
,
Delphine Le Corre
(1)
,
Sanam Peyvandi
(3, 4)
,
Claire Mulot
(1, 5)
,
Ralph Niarra
(6)
,
Pascaline Aucouturier
(6)
,
Gilles Chatellier
(6)
,
Philippe Nizard
(1)
,
Karla Perez-Toralla
(1)
,
Eleonora Zonta
(1)
,
Cécile Charpy
(3, 4)
,
Anaïs Pujals
(7, 8)
,
Caroline Barau
(8)
,
Olivier Bouché
(9)
,
Jean-François Emile
(10)
,
Denis Pezet
(11)
,
Frédéric Bibeau
(12)
,
J Brian Hutchison
(13)
,
Darren R. Link
(13)
,
Aziz Zaanan
(1, 2)
,
Pierre Laurent-Puig
(1, 14)
,
Iradj Sobhani
(3, 4)
,
Valérie Taly
(1)
1
MEPPOT - U1147 -
Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 EC2M3 - Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375)
4 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
5 Centre Universitaires des Saints-Pères
6 Centre d'Investigation Clinique
7 IMRB - Institut Mondor de Recherche Biomédicale
8 Hôpital Henri Mondor
9 CHU Reims - Hôpital universitaire Robert Debré [Reims]
10 Service de pathologie [CHU Ambroise Paré]
11 CHU Clermont-Ferrand
12 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
13 RainDance Technologies, Inc.
14 Service de biologie [CHU HEGP]
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 EC2M3 - Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375)
4 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
5 Centre Universitaires des Saints-Pères
6 Centre d'Investigation Clinique
7 IMRB - Institut Mondor de Recherche Biomédicale
8 Hôpital Henri Mondor
9 CHU Reims - Hôpital universitaire Robert Debré [Reims]
10 Service de pathologie [CHU Ambroise Paré]
11 CHU Clermont-Ferrand
12 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
13 RainDance Technologies, Inc.
14 Service de biologie [CHU HEGP]
Audrey Didelot
- Fonction : Auteur
- PersonId : 1005225
Delphine Le Corre
- Fonction : Auteur
- PersonId : 855598
Gilles Chatellier
- Fonction : Auteur
- PersonId : 757348
- ORCID : 0000-0002-6373-8956
Caroline Barau
- Fonction : Auteur
- PersonId : 745878
- IdHAL : caroline-barau
- ORCID : 0000-0003-4289-3276
- IdRef : 140155678
Jean-François Emile
- Fonction : Auteur
- PersonId : 757060
- ORCID : 0000-0002-6073-4466
- IdRef : 105749788
Pierre Laurent-Puig
- Fonction : Auteur
- PersonId : 757353
- ORCID : 0000-0001-8475-5459
- IdRef : 071013512
Iradj Sobhani
- Fonction : Auteur
- PersonId : 1387570
- ORCID : 0000-0002-5113-0660
Valérie Taly
- Fonction : Auteur
- PersonId : 177600
- IdHAL : valerie-taly
- ORCID : 0000-0002-3116-8602
- IdRef : 161486983
Résumé
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.