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1. CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC)

Author

Sefrioui, David, Beaussire, Ludivine, Gillibert, André, Blanchard, France, Toure, Emmanuel, Bazille, Céline, Perdrix, Anne, Ziegler, Frédéric, Gangloff, Alice, Hassine, Mélanie, Elie, Caroline, Bignon, Anne-Laure, Parzy, Aurélie, Gomez, Philippe, Thill, Caroline, Clatot, Florian, Sabourin, Jean-Christophe, Frebourg, Thierry, Benichou, Jacques, Bouhier-Leporrier, Karine, Gallais, Marie-Pierre, Sarafan-Vasseur, Nasrin, Michel, Pierre, and Di Fiore, Frédéric

Published
2021
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11. Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer

Author

Sefrioui , France, Vermeulin , France, Blanchard , France, Chapusot , Caroline, Beaussire , Ludivine, Armengol-Debeir , Laura, Sesboué , Richard, Gangloff , Alice, Hebbar , Mohamed, Copin , Marie-Christine, Houivet , Estelle, Schwarz , Lilian, Clatot , Florian, Tuech , Jacques, Bénichou , Jacques, Martin , Laurent, Bouvier , Anne-Marie, Sabourin , Jean-Christophe, Sarafan-Vasseur , Nasrin, Frébourg , Thierry, Lepage , Côme, Michel , Pierre, Di Fiore , Frédéric, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Hôpital Charles Nicolle [Tunis], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pathologie, PRES Université Lille Nord de France-Faculté de Médecine Henri Warembourg-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Charles Nicolle [Rouen], Groupe d'étude des proliférations lymphoïdes (GPL), Unité de biostatistiques [CHU Rouen], Centre Guillaume le Conquérant, Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [Rouen], Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [CHU Lille], Département de chirurgie [Rouen], CRLCC Henri Becquerel, Service de chirurgie digestive [Rouen], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Oncologie Médicale, and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel )

Subjects
Male, Proto-Oncogene Proteins B-raf, MESH: Colon Cancer, DNA Copy Number Variations, Receptor, ErbB-2, MESH: Chromosomal instability, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, MESH: Copy Number Variation, Loss of Heterozygosity, Receptors, Cell Surface, Polymerase Chain Reaction, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Humans, Prospective Studies, Neoplasm Metastasis, Aged, Proportional Hazards Models, Colon Cancer, Tumor Suppressor Proteins, Carcinoma, Middle Aged, DCC Receptor, Prognosis, Copy Number Variation, Chromosomal instability, Microstellite Stable, Phenotype, Treatment Outcome, Colonic Neoplasms, MESH: Disease-Free Survival, Female, MESH: Microstellite Stable, Neoplasm Recurrence, Local, Microsatellite Repeats
Abstract

IF 5.531; International audience; We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p

Published
2017
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12. An improved assay for detection of theranostic gene translocations and METexon 14 skipping in thoracic oncology

Author

Piton, Nicolas, Lanic, Marie-Delphine, Marguet, Florent, Lamy, Aude, Blanchard, France, Guisier, Florian, Viennot, Mathieu, Salaün, Mathieu, Thiberville, Luc, Jardin, Fabrice, Sabourin, Jean-Christophe, and Ruminy, Philippe

Abstract

Theranostic translocations may be difficult to detect by routine techniques, especially when specimens are exiguous. We recently demonstrated in a series of translocated lung adenocarcinomas that LD-RT-PCR (ligation-dependent reverse transcription polymerase chain reaction) assay could identify ALK, ROS1and RETrearrangements with 64% sensitivity and 100% specificity. Here, we report an upgraded version of this assay used in a routine prospective cohort of lung carcinomas. Newly diagnosed lung carcinomas referred to the Rouen molecular platform between 15/05/2018 and 15/05/2019 for ALK and ROS1 IHC, genotyping (SNaPshot© +/− high-throughput genotyping) and sometimes FISH (standard routine process) were tested prospectively in parallel with the LD-RT-PCR assay designed to detect at one go ALK, ROS1and RETtranslocations and METexon 14 skipping. 413 tumors from 396 patients were included. LD-RT-PCR had a global sensitivity of 91.43% (standard routine process: 80%), with a specificity of 100%. It detected 15/18 ALKand 4/4 ROS1translocated tumors, but also 6/6 tumors with METexon 14 skipping retrieved by genotyping. In addition, it retrieved 7 alterations missed by the routine process, then confirmed by other means: 5 METexon 14 skipping and 2 RETtranslocated tumors. Finally, it allowed to deny an effect on METexon 14 skipping for 8 mutations detected by routine genotyping. We successfully implemented LD-RT-PCR in routine analysis. This technique is cheap, fast, sensitive, specific, and easily upgradable (e.g., NTRKtranslocations), but still requires IHC to be performed in parallel. Owing to its advantages, we recommend considering it, in parallel with IHC and genotyping, as an excellent cost-effective alternative, for the systematic testing of lung adenocarcinoma, to FISH and to more expensive and complex assays such as RNA-seq.

Published
2021
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13. Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

Author

Sefrioui, David, primary, Blanchard, France, additional, Toure, Emmanuel, additional, Basile, Paul, additional, Beaussire, Ludivine, additional, Dolfus, Claire, additional, Perdrix, Anne, additional, Paresy, Marianne, additional, Antonietti, Michel, additional, Iwanicki-Caron, Isabelle, additional, Alhameedi, Raied, additional, Lecleire, Stephane, additional, Gangloff, Alice, additional, Schwarz, Lilian, additional, Clatot, Florian, additional, Tuech, Jean-Jacques, additional, Frébourg, Thierry, additional, Jardin, Fabrice, additional, Sabourin, Jean-Christophe, additional, Sarafan-Vasseur, Nasrin, additional, Michel, Pierre, additional, and Di Fiore, Frédéric, additional

Published
2017
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14. Copy number variations in DCC/18q and ERBB2/17q are associated with disease‐free survival in microsatellite stable colon cancer

Author

Sefrioui, David, primary, Vermeulin, Thomas, additional, Blanchard, France, additional, Chapusot, Caroline, additional, Beaussire, Ludivine, additional, Armengol‐Debeir, Laura, additional, Sesboué, Richard, additional, Gangloff, Alice, additional, Hebbar, Mohamed, additional, Copin, Marie‐Christine, additional, Houivet, Estelle, additional, Schwarz, Lilian, additional, Clatot, Florian, additional, Tuech, Jean‐Jacques, additional, Bénichou, Jacques, additional, Martin, Laurent, additional, Bouvier, Anne‐Marie, additional, Sabourin, Jean‐Christophe, additional, Sarafan‐Vasseur, Nasrin, additional, Frébourg, Thierry, additional, Lepage, Côme, additional, Michel, Pierre, additional, and Di Fiore, Frédéric, additional

Published
2017
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15. Prospective analysis of CEA, circulating DNA (cDNA) and circulating tumor cells (CTC) kinetics in patients (pts) treated for a metastatic colorectal cancer (mCRC).

Author

Sefrioui, David, primary, Sarafan-Vasseur, Nasrin, additional, Toure, Emmanuel, additional, Delacour, Julien, additional, Ziegler, Frederic, additional, Thill, Caroline, additional, Gangloff, Alice, additional, Blanchard, France, additional, Beaussire, Ludivine, additional, Bouhier Leporrier, Karine, additional, Galais, Marie-Pierre, additional, Perdrix, Anne, additional, Clatot, Florian, additional, Jardin, Fabrice, additional, Sabourin, Jean-Christophe, additional, Frébourg, Thierry, additional, Michel, Pierre, additional, and Di Fiore, Frédéric, additional

Published
2016
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17. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer

Author

Boissière-Michot, Florence, primary, Lazennec, Gwendal, additional, Frugier, Hélène, additional, Jarlier, Marta, additional, Roca, Lise, additional, Duffour, Jacqueline, additional, Du Paty, Emilie, additional, Laune, Daniel, additional, Blanchard, France, additional, Le Pessot, Florence, additional, Sabourin, Jean-Christophe, additional, and Bibeau, Frédéric, additional

Published
2014
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18. Genetic variations of the A13/A14 repeat located within the EGFR3′ untranslated region have no oncogenic effect in patients with colorectal cancer

Author

Sarafan-Vasseur, Nasrin, primary, Sefrioui, David, additional, Tougeron, David, additional, Lamy, Aude, additional, Blanchard, France, additional, Le Pessot, Florence, additional, Di Fiore, Frédéric, additional, Michel, Pierre, additional, Bézieau, Stéphane, additional, Latouche, Jean-Baptiste, additional, Frebourg, Thierry, additional, and Sesboüé, Richard, additional

Published
2013
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19. Usefulness of circulating tumor cell detection in pancreatic adenocarcinoma diagnosis.

Author

Basile, Paul, primary, iwanicki-Caron, Isabelle, additional, Toure, Emmanuel, additional, Antonietti, Michel, additional, Lecleire, Stephane, additional, Di Fiore, Aude, additional, oden-Gangloff, Alice, additional, Blanchard, France, additional, Lemoine, Francoise, additional, Di Fiore, Frédéric, additional, Sabourin, Jean-Christophe, additional, and Michel, Pierre, additional

Published
2013
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20. Usefulness of Circulating Tumor Cell Detection in Pancreatic Adenocarcinoma Diagnosis

Author

Iwanicki-Caron, Isabelle, primary, Basile, Paul, additional, Toure, Emmanuel, additional, Antonietti, Michel, additional, Lecleire, Stephane, additional, Di Fiore, Aude, additional, Oden-Gangloff, Alice, additional, Blanchard, France, additional, Lemoine, Francoise, additional, Di Fiore, Frederic, additional, Sabourin, Jean Christophe, additional, and Michel, Pierre, additional

Published
2013
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22. Abstract 317: Colorectal cancers with microsatellite instability harbor an inflammatory microenvironment, different from the one observed in microsatellite stable colorectal cancers

Author

Bibeau, Frédéric, primary, Lazennec, Gwendal, additional, Frugier, Hélène, additional, Jarlier, Marta, additional, Roca, Lise, additional, Laune, Daniel, additional, Blanchard, France, additional, Lamy, Aude, additional, Pessot, Florence Le, additional, Sabourin, Jean-Christophe, additional, and Boissiere-Michot, Florence, additional

Published
2012
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24. Usefulness of circulating tumor cell detection for the diagnosis of malignant pancreatic head tumors: A pilot study.

Author

Coget, Julien, primary, Blanchard, France, additional, Lamy, Aude, additional, Toure, Emmanuel, additional, Chiavelli, Helene, additional, Basile, Paul, additional, Di Fiore, Frédéric, additional, iwanicki-Caron, Isabelle, additional, Michel, Pierre, additional, Lemoine, Francoise, additional, and Sabourin, Jean-Christophe, additional

Published
2012
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25. Impact of FcγRIIa-FcγRIIIa Polymorphisms and KRAS Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan

Author

Bibeau, Frédéric, primary, Lopez-Crapez, Evelyne, additional, Di Fiore, Frédéric, additional, Thezenas, Simon, additional, Ychou, Marc, additional, Blanchard, France, additional, Lamy, Aude, additional, Penault-Llorca, Frédérique, additional, Frébourg, Thierry, additional, Michel, Pierre, additional, Sabourin, Jean-Christophe, additional, and Boissière-Michot, Florence, additional

Published
2009
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27. Genetic variations of the A13/A14 repeat located within the EGFR 3' untranslated region have no oncogenic effect in patients with colorectal cancer.

Author

Sarafan-Vasseur, Nasrin, Sefrioui, David, Tougeron, David, Lamy, Aude, Blanchard, France, Pessot, Florence Le, Fiore, Frédéric Di, Michel, Pierre, Bézieau, Stéphane, Latouche, Jean-Baptiste, Frebourg, Thierry, and Sesboüé, Richard

Subjects
HUMAN genetic variation, GENETIC mutation, GENETIC polymorphisms, COLON cancer, CELL culture, MESSENGER RNA
Abstract

Background: The EGFR 3' untranslated region (UTR) harbors a polyadenine repeat which is polymorphic (A13/A14) and undergoes somatic deletions in microsatellite instability (MSI) colorectal cancer (CRC). These mutations could be oncogenic in colorectal tissue since they were shown to result into increased EGFR mRNA stability in CRC cell lines. Methods: First, we determined in a case control study including 429 CRC patients corresponding to different groups selected or not on age of tumor onset and/or familial history and/or MSI, whether or not, the germline EGFR A13/A14 polymorphism constitutes a genetic risk factor for CRC; second, we investigated the frequency of somatic mutations of this repeat in 179 CRC and their impact on EGFR expression. Results: No statistically significant difference in allelic frequencies of the EGFR polyA repeat polymorphism was observed between CRC patients and controls. Somatic mutations affecting the EGFR 3'UTR polyA tract were detected in 47/80 (58.8%) MSI CRC versus 0/99 microsatellite stable (MSS) tumors. Comparative analysis in 21 CRC samples of EGFR expression, between tumor and non malignant tissues, using two independent methods showed that somatic mutations of the EGFR polyA repeat did not result into an EGFR mRNA increase. Conclusion: Germline and somatic genetic variations occurring within the EGFR 3' UTR polyA tract have no impact on CRC genetic risk and EGFR expression, respectively. Genotyping of the EGFR polyA tract has no clinical utility to identify patients with a high risk for CRC or patients who could benefit from anti-EGFR antibodies [ABSTRACT FROM AUTHOR]

Published
2013
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28. Metastatic colorectal cancer KRASgenotyping in routine practice: results and pitfalls

Author

Lamy, Aude, Blanchard, France, Le Pessot, Florence, Sesboüé, Richard, Di Fiore, Frédéric, Bossut, Jessie, Fiant, Elodie, Frébourg, Thierry, and Sabourin, Jean-Christophe

Abstract

KRASgenotyping is mandatory before anti-epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer, which is the second leading cause of cancer-related death in the United States and in Europe. Thus, large-scale KRASmutation screening is needed for efficient patient management and in the future metastatic colorectal cancer genotyping might also include the detection of the BRAFV600E mutation, which is a very strong negative prognostic factor in colorectal cancer. We report our experience of routine KRAS/BRAFmutation screening practice performed on 1130 formalin-fixed paraffin-embedded tumor samples from 992 colorectal cancer patients. DNA was extracted from macrodissected tumor areas highlighted by a pathologist, KRAScodons 12/13 and BRAFV600E mutations were assessed in a single SNaPshot® multiplex assay and each mutation was confirmed by an independent analysis. KRASand BRAFmutations were, respectively, present in 41.8 and 6.5% of the tumor samples. If KRASand BRAFmutations were mutually exclusive, four samples presented two concomitant KRASmutations. Genotyping of paired primary tumors and metastases from 44 patients indicated that 5 patients (11.4%) presented discordant KRASmutational status. KRASgenotype heterogeneity was also observed within primary tumor sites in seven cases. Non-reproducible KRASartefactual mutations were detected in 53 samples (4.7%). We found that the prominent mechanism leading to these artefactual mutations was the fragmentation of DNA occurring during tissue processing. Routine KRASgenotyping performed on formalin-fixed paraffin-embedded tissues requires, therefore, the development of quality control scheme for molecular pathology, especially because of DNA damages induced by formalin fixation. The tumor heterogeneity observed in some patients indicates that it should be more appropriate to perform KRASgenotyping on metastases if sample is available.

Published
2011
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29. Contribution of the BOP1 gene, located on 8q24, to colorectal tumorigenesis.

Author

Killian A, Sarafan-Vasseur N, Sesboüé R, Le Pessot F, Blanchard F, Lamy A, Laurent M, Flaman JM, and Frébourg T

Subjects
Gene Dosage, HeLa Cells, Humans, Neoplasm Proteins biosynthesis, Neoplasm Proteins physiology, Nuclear Proteins biosynthesis, Nuclear Proteins genetics, Nuclear Proteins physiology, RNA-Binding Proteins, Ribosomal Protein L3, Chromosomes, Human, Pair 8, Colorectal Neoplasms genetics, Neoplasm Proteins genetics, Proteins genetics, Signal Transduction genetics
Abstract

The most common form of genomic instability observed in colorectal cancer is chromosomal instability (CIN), whose molecular bases remain to be determined. We have previously demonstrated that inactivation in human cells of several components of the Pes1-Bop1 complex (BOP1, GRWD1, PES1, ORC6L, and RPL3), involved in ribosome biogenesis, altered chromosome segregation. To determine the contribution to colorectal tumorigenesis of somatic alterations of genes involved in ribosome biogenesis, we screened 56 primary colorectal cancers, using quantitative multiplex PCR of short fluorescent fragments, a sensitive method for the detection of gene dosage alterations. We found that dosage increase of the BOP1 gene was a frequent event, being detected in 39% of the tumors, and we show that it is associated with an increase of BOP1 mRNA. Scanning of 8q24, on which BOP1 is located, revealed that in colorectal cancers, gene dosage increase of BOP1 can be independent from that of MYC and was more frequent than that affecting MYC. Finally, transient overexpression of BOP1 in human cells increased the percentage of multipolar spindles. Together with our previous results, the present study strongly suggests that deregulation of the BOP1 pathway contributes to colorectal tumorigenesis., ((c) 2006 Wiley-Liss, Inc.)

Published
2006
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