Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil–based chemotherapy.

Collura, Ada; Lagrange, Anaïs; Svrcek, Magali; Marisa, Laetitia; Buhard, Olivier; Guilloux, Agathe; Wanherdrick, Kristell; Dorard, Coralie; Taieb, Anna; Saget, Arnaud; Loh, Marie; Soong, Richie; Zeps, Nikolajs; Platell, Cameron; Mews, Andrew; Iacopetta, Barry; De Thonel, Aurélie; Seigneuric, Renaud; Marcion, Guillaume; Chapusot, Caroline; Lepage, Come; Bouvier, Anne-Marie; Gaub, Marie-Pierre; Milano, Gérard; Selves, Janick; Senet, Patrick; Delarue, Patrice; Arzouk, Hayat; Lacoste, Claire; Coquelle, Arnaud; Bengrine-Lefèvre, Leila; Tournigand, Christophe; Lefèvre, Jérémie H; Parc, Yann; Biard, Denis S; Fléjou, Jean-François; Garrido, Carmen; Duval, Alex

doi:10.1053/j.gastro.2013.10.054

Article (Scientific journals)

Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil–based chemotherapy.

Collura, Ada; Lagrange, Anaïs; Svrcek, Magali et al.

2014 • In Gastroenterology, 146 (2), p. 401-11.e1

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/291338

DOI
10.1053/j.gastro.2013.10.054

PubMed
24512910

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Keywords :

Antineoplastic Agents; Biomarkers, Tumor; HSP110 Heat-Shock Proteins; Organoplatinum Compounds; Oxaliplatin; Leucovorin; Fluorouracil; Aged; Antineoplastic Agents/administration & dosage; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Biomarkers, Tumor/chemistry; Biomarkers, Tumor/genetics; Biomarkers, Tumor/metabolism; Blotting, Western; Cell Line, Tumor; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms/drug therapy; Colorectal Neoplasms/genetics; Colorectal Neoplasms/mortality; Colorectal Neoplasms/surgery; Female; Fluorouracil/administration & dosage; Follow-Up Studies; HSP110 Heat-Shock Proteins/chemistry; HSP110 Heat-Shock Proteins/genetics; HSP110 Heat-Shock Proteins/metabolism; Humans; Introns; Leucovorin/administration & dosage; Male; Models, Molecular; Organoplatinum Compounds/administration & dosage; Retrospective Studies; Surface Plasmon Resonance; Survival Analysis; Treatment Outcome; Base Sequence; Microsatellite Instability; Sequence Deletion; Outcome; Prognostic Factor; Therapeutic Response; Treatment; Hepatology; Gastroenterology

Abstract :

[en] BACKGROUND & AIMS: Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses than patients with tumors without MSI, but have a poor response to 5-fluorouracil–based chemotherapy. A dominant-negative form of heat shock protein (HSP)110 (HSP110DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T(17) intron repeat, sensitizes the cells to 5-fluorouracil and oxaliplatin.We investigated whether HSP110 T(17) could be used to identify patients with colorectal cancer who would benefit from adjuvant chemotherapy with 5-fluorouracil and oxaliplatin. METHODS: We characterized the interaction between HSP110 and HSP110DE9 using surface plasmon resonance. By using polymerase chain reaction and fragment analysis, we examined how the size of somatic allelic deletions in HSP110 T(17) affected the HSP110 protein expressed by tumor cells. We screened 329 consecutive patients with stage II–III colorectal tumors with MSI who underwent surgical resection at tertiary medical centers for HSP110 T(17). RESULTS: HSP110 and HSP110DE9 interacted in a1:1 ratio. Tumor cells with large deletions in T(17) had increased ratios of HSP110DE9:HSP110, owing to the loss of expression of full-length HSP110. Deletions in HSP110 T(17) were mostly biallelic in primary tumor samples with MSI. Patients with stage II–III cancer who received chemotherapy and had large HSP110 T(17) deletions (≥5 bp; 18 of 77 patients, 23.4%) had longer times of relapse-free survival than patients with small or no deletions (≤4 bp; 59 of 77 patients, 76.6%) in multivariate analysis (hazard ratio, 0.16; 95% confidence interval, 0.012–0.8; P = .03). We found a significant interaction between chemotherapy and T17 deletion (P =.009). CONCLUSIONS: About 25% of patients with stages II–III colorectal tumors with MSI have an excellent response to chemotherapy, due to large, biallelic deletions in the T(17) intron repeat of HSP110 in tumor DNA.

Disciplines :

Gastroenterology & hepatology

Author, co-author :

Collura, Ada; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Lagrange, Anaïs; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Svrcek, Magali; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France ; AP-HP, Hôpital Saint-Antoine, Service d'Anatomie et Cytologie Pathologiques, Paris, France ; Plateforme de Microdissection de l'Institut Federatif de Recherche 65 et Tumorotheque, Hôpitaux Universitaires Paris-Est, Paris, France

Marisa, Laetitia; Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France

Buhard, Olivier; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Guilloux, Agathe; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Wanherdrick, Kristell; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Dorard, Coralie; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Taieb, Anna; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

Saget, Arnaud; INSERM UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, 75012 Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France

More authors (28 more)

Language :

English

Title :

Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil–based chemotherapy.

Publication date :

February 2014

Journal title :

Gastroenterology

ISSN :

0016-5085

eISSN :

1528-0012

Publisher :

W.B. Saunders, United States

Volume :

146

Issue :

Pages :

401-11.e1

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S001650851301528X?httpAccept=text/xml

Funding text :

Funding This work was supported by the Carte d'Identité des Tumeurs program (available: http://cit.ligue-cancer.net ) from the Ligue Nationale Contre le Cancer and by grants from the Institut National du Cancer (A.D.), AD group has the label de « La Ligue Contre le Cancer », an Institut National du Cancer fellowship (A.C.), and a Ministère de l'Enseignement Supérieur et de le Recherche fellowship (A.L.). No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Bibliography

L.A. Aaltonen, P. Peltomaki, and F.S. Leach et al. Clues to the pathogenesis of familial colorectal cancer Science 260 1993 812 816
Y. Ionov, M.A. Peinado, and S. Malkhosyan et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis Nature 363 1993 558 561
R. Fishel, M.K. Lescoe, and M.R. Rao et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer Cell 75 1993 1027 1038
C.M. Ribic, D.J. Sargent, and M.J. Moore et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer N Engl J Med 349 2003 247 257
J.M. Carethers, E.J. Smith, and C.A. Behling et al. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer Gastroenterology 126 2004 394 401
D.J. Sargent, S. Marsoni, and G. Monges et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer J Clin Oncol 28 2010 3219 3226
C. Dorard, A. de Thonel, and A. Collura et al. Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis Nat Med 17 2011 1283 1289
M. Kai, T. Nakatsura, and H. Egami et al. Heat shock protein 105 is overexpressed in a variety of human tumors Oncol Rep 10 2003 1777 1782
O. Slaby, K. Sobkova, and M. Svoboda et al. Significant overexpression of Hsp110 gene during colorectal cancer progression Oncol Rep 21 2009 1235 1241
A.L. Rerole, J. Gobbo, and A. De Thonel et al. Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy Cancer Res 71 2011 484 495
J.P. Schuermann, J. Jiang, and J. Cuellar et al. Structure of the Hsp110:Hsc70 nucleotide exchange machine Mol Cell 31 2008 232 243
A. Sali, and T.L. Blundell Comparative protein modelling by satisfaction of spatial restraints J Mol Biol 234 1993 779 815
D.S. Biard, E. Despras, and A. Sarasin et al. Development of new EBV-based vectors for stable expression of small interfering RNA to mimick human syndromes: application to NER gene silencing Mol Cancer Res 3 2005 519 529
N. Suraweera, A. Duval, and M. Reperant et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR Gastroenterology 123 2002 1804 1811
O. Buhard, F. Cattaneo, and Y.F. Wong et al. Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors J Clin Oncol 24 2006 241 251
H. Hampel, W.L. Frankel, and E. Martin et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer) N Engl J Med 352 2005 1851 1860
M. Svrcek, O. Buhard, and C. Colas et al. Methylation tolerance due to an O6-methylguanine DNA methyltransferase (MGMT) field defect in the colonic mucosa: an initiating step in the development of mismatch repair-deficient colorectal cancers Gut 59 2010 1516 1526
M. Svrcek, J. El-Bchiri, and A. Chalastanis et al. Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability J Clin Oncol 25 2007 4231 4238
T. Andre, C. Boni, and L. Mounedji-Boudiaf et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer N Engl J Med 350 2004 2343 2351
M.M. Weiss, M.A. Hermsen, and G.A. Meijer et al. Comparative genomic hybridisation Mol Pathol 52 1999 243 251
J. El-Bchiri, A. Guilloux, and P. Dartigues et al. Nonsense-mediated mRNA decay impacts MSI-driven carcinogenesis and anti-tumor immunity in colorectal cancers PLoS One 3 2008 e2583
Y. Ionov, N. Nowak, and M. Perucho et al. Manipulation of nonsense mediated decay identifies gene mutations in colon cancer cells with microsatellite instability Oncogene 23 2004 639 645
D.G. Altman, B. Lausen, and W. Sauerbrei et al. Dangers of using "optimal" cutpoints in the evaluation of prognostic factors J Natl Cancer Inst 86 1994 829 835
S. Markowitz, J. Wang, and L. Myeroff et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability Science 268 1995 1336 1338
C. Colas, F. Coulet, and M. Svrcek et al. Lynch or not Lynch? Is that always a question? Adv Cancer Res 113 2012 121 166
P.G. Gavin, L.H. Colangelo, and D. Fumagalli et al. Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value Clin Cancer Res 18 2012 6531 6541
F.A. Sinicrope, N.R. Foster, and S.N. Thibodeau et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy J Natl Cancer Inst 103 2011 863 875
J.F. You, O. Buhard, and M.J. Ligtenberg et al. Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats Br J Cancer 103 2010 1840 1845
J.H. Kim, K.J. Kim, and Y.Y. Rhee et al. Expression status of wild-type HSP110 correlates with HSP110 T deletion size and patient prognosis in microsatellite-unstable colorectal cancer Mod Pathol 2013 Epub ahead of print