Fondation MEDIC

www.fondation-medic.ch

Linking tumor heterogeneity with clinically useful subtypes of colon cancer
[19.10.2016]
Project leader – Mauro Delorenzi
Mauro Delorenzi

Mauro Delorenzi received a M.Sc in molecular biology and one in statistics from Zürich University, where he also completed a PhD in 1989 in molecular genetics. He started bioinformatics analysis of DNA and protein sequences during a postdoctoral training at the Walter and Eliza Hall Institute in Melbourne, Australia.
In 2002 he was hired into the NCCR Molecular Oncology program at ISREC in Lausanne, Switzerland.

Since 2003 he leads the Lausanne Bioinformatics Core Facility, which is run predominantly as part of the SIB Swiss Institute of Bioinformatics.
Since 2013, Mauro Delorenzi is associated to the Ludwig Center for Cancer Research of the University of Lausanne and to the new Swiss Cancer Center Lausanne.

Office 2021, Génopode Building, Quartier Sorge
CH-1015 Lausanne

Tel: +41 21 692 40 97
Fax: +41 21 692 40 55

E-Mail: mauro.delorenzi@unil.ch

Laboratory web page

Group members
 

Paolo Angelino PhD

bioinformatician

Pierre Bady PhD

senior scientist

David Barras PhD

postdoctoral fellow

Pamela Dobay PhD

postdoctoral fellow

Delphine Grun

bioinformatician

Dirk Klingbiel PhD

senior scientist (most at SAKK)

Frédéric Schütz PhD

senior scientist

Petros Tsantoulis MD

senior scientist

Pratyaksha Asa Wirapati PhD

senior scientist

Nadine Zangger PhD

bioinformatician

Alix Zollinger PhD

bioinformatician-statistician

Project description
 

Bioinformatics Core Facility (BCF)

Group presentation

The group of Mauro Delorenzi is specialised in the application of statistical and bioinformatics methods in biological data analysis, with a focus on new technologies and on molecular and medical translational research.
The core competence and activities reside in the interface between biomedical sciences, statistics and computation, particularly in the application of high-throughput omics technologies, such as gene-expression microarray, to problems of clinical importance, such as development of cancer biomarkers. The BCF also offers consulting, teaching and training, data analysis support and research collaborations for both academic and industrial partners.

The most important projects include the analysis of deep sequencing chip-seq data of the CycliX consortium, collaborations with the research groups of M. Hegi (glioblastoma), L. de Leval (T cell lymphomas), S. Tejpar (colorectal cancer) and T. Petrova (colon cancer and PROX1 transcription factor).
The group participates to international cancer collaborations, in particular in colon cancer (EU’s Coltheres consortium), as well as in method and infrastructure development (EU’s P-Medicine consortium).

We are also interested in testing tumor risk scores proposed by other researchers in independent data to understand which one are really useful, how they can be combined among themselves and with known prognostic factors and to work out implications for patient management and personalized treatment optimization.

figure 1
Heatmap showing the patterns of differential gene expression used to define 5 subtypes (A-E) of CRC, in comparison with normal reference tissue (N). On the left short biological description of the gene functions.

Molecular heterogeneity of colorectal cancer

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS , BRAF). Attempts to fill this gap are emerging.

We have contributed to clarifying the role of mutations in key genes for application as prognostic and predictive markers. In the analysis of gene expression profiles, we have discovered that a very specific pattern is associated with tumors that carry activating BRAF mutations. This pattern is shared with a set of additional tumors, which show similar characteristics, and in particular very poor survival in the metastatic setting. It thus identifies a very interesting group for whom new treatments are required.

Following up on this study, we have been developing a system for classifying colon cancer cases into separate "prototypical" groups. The approach chosen is to establish a system of several typical subtype patterns in gene expression and to then associate each new tumor with the most similar subtype. The subtypes might be due to different tumor development histories. They show different biological characteristics, some of likely clinical relevance, such as risk of relapse and sensitivity to different pathway-inhibition directed drug treatments.

We performed a prior free analysis of CRC heterogeneity on over 1'000 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed.

A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided a classification beyond what all other variables could provide. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles.

figure 2
Characteristics associated with the CRC subtypes and normal reference tissue gene expression groups.

The subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets for their association with treatment efficacy. If sufficiently robust, they could be prospectively assessed for clinical relevance in terms of prognosis and personalized treatment decision making.

We plan to continue this line of research in a wide international collaboration with the aim to generate a consensus subtyping system for colorectal cancer, with participation of various teams that have published similar studies.

Collaboration with other MEDIC partners

In addition to this main project, we bring bioinformatics, computing and statistic support to several other MEDIC projects.
We contribute to the research effort of Laurence de Laval and her group, to characterize molecular biomarkers relevant to the diagnosis and prognosis of nodal peripheral T-cell lymphomas. In this project, we attempt to identify subgroups in these rare malignancies, based on gene expression patterns. Understanding the molecular mechanisms underlying these subgroups might have important implications for diagnosis and response to therapy.
We also bring bioinformatics support to the group of Tatiana Petrova in the study of mechanisms involved in colon cancer metastasis formation and growth. Petrova's lab is particularly interested in the role of PROX1, a gene involved in the interaction between the cancer cells and the host stromal cells, closely associated with the signaling pathway involved in regulation of cell differentiation in intestinal mucosa (the Wnt pathway) and also in transformation of intestinal epithelial cells into cancer cells. Recent experiments suggest that PROX1 is involved in progression to later stages (e.g.metastasis) rather than in the initial stages of colorectal cancer development. We try to uncover the molecular mechanisms by which PROX1 may influence metastatic formation or growth by the bioinformatics analysis of gene expression experiments, when PROX1 is up- or down-regulated.

figure 3

Publications
 
2016 / 10.1016/j.ebiom.2016.01.019
Scholz G, Jandus C, Zhang L, Grandclément C, Lopez-Mejia IC, Soneson C, Delorenzi M, Fajas L, Held W, Dormond O, Romero P. Modulation of mTOR Signalling Triggers the Formation of Stem Cell-like Memory T Cells. EBioMedicine. 2016;4:50-61
» PubMed
2015 / 10.1126/scitranslmed.aaa3700
Fuertes Marraco SA, Soneson C, Cagnon L, Gannon PO, Allard M, Maillard SA, Montandon N, Rufer N, Waldvogel S, Delorenzi M, Speiser DE. Long-lasting stem cell-like memory CD8+ T cells with a naďve-like profile upon yellow fever vaccination. Sci Transl Med. 2015 Apr 8;7(282):282ra48
» PubMed
2015 / 10.1158/1078-0432
Schell MJ, Yang M, Missiaglia E, Delorenzi M, Soneson C, Yue B, Nebozhyn MV, Loboda A, Bloom G, Yeatman TJ. A Composite Gene Expression Signature Optimizes Prediction of Colorectal Cancer Metastasis and Outcome. Clin Cancer Res. 2016 Feb 1;22(3):734-45
» PubMed
2015 / PMID: 25305506
Sinicrope FA, Shi Q, Smyrk TC, Thibodeau SN, Dienstmann R, Guinney J, Bot BM, Tejpar S, Delorenzi M, Goldberg RM, Mahoney M, Sargent DJ, Alberts SR. Molecular Markers Identify Subtypes of Stage III Colon Cancer Associated With Patient Outcomes. Gastroenterology. 2015 Jan;148(1):88-99
» PubMed
2015 / doi: 10.1038/ng.3362. PMID: 26214592.
Fischer U, Forster M, Rinaldi A, Risch T, Sungalee S, Warnatz HJ, Bornhauser B, Gombert M, Kratsch C, Stütz AM, Sultan M, Tchinda J, Worth CL, Amstislavskiy V, Badarinarayan N, Baruchel A, Bartram T, Basso G, Canpolat C, Cario G, Cavé H, Dakaj D, Delorenzi M, Dobay MP, Eckert C, Ellinghaus E, Eugster S, Frismantas V, Ginzel S, Haas OA, Heidenreich O, Hemmrich-Stanisak G, Hezaveh K, Höll JI, Hornhardt S, Husemann P, Kachroo P, Kratz CP, Kronnie GT, Marovca B, Niggli F, McHardy AC, Moorman AV, Panzer-Grümayer R, Petersen BS, Raeder B, Ralser M, Rosenstiel P, Schäfer D, Schrappe M, Schreiber S, Schütte M, Stade B, Thiele R, Weid NV, Vora A, Zaliova M, Zhang L, Zichner T, Zimmermann M, Lehrach H, Borkhardt A, Bourquin JP, Franke A, Korbel JO, Stanulla M, Yaspo ML. Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nat Genet. 2015 Jul 27.
» PubMed
2015 / 10.1158/1078-0432
Hingorani P, Missiaglia E, Shipley J, Anderson JR, Triche TJ, Delorenzi M, Gastier-Foster J, Wing M, Hawkins DS, Skapek SX. Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group. Clin Cancer Res. 2015 15;21(20):4733-9.
» PubMed
2015 / doi: 10.1016/j.molonc.2015.02.008. PMID: 25759163.
Jensen NF, Stenvang J, Beck MK, Hanáková B, Belling KC, Do KN, Viuff B, Nygĺrd SB, Gupta R, Rasmussen MH, Tarpgaard LS, Hansen TP, Budinská E, Pfeiffer P, Bosman F, Tejpar S, Roth A, Delorenzi M, Andersen CL, Rřmer MU, Brünner N, Moreira JM. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance. Mol Oncol. 2015 Feb 24
» PubMed
2015 / 10.1038/srep15375
De Meyer T, Bady P, Trooskens G, Kurscheid S, Bloch J, Kros JM, Hainfellner JA, Stupp R, Delorenzi M, Hegi ME, Van Criekinge W. Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison. Sci Rep. 2015 Oct 20;5:15375.
» PubMed
2015 / PMID: 25361982.
Klingbiel D, Saridaki Z, Roth AD, Bosman F, Delorenzi M, Tejpar S. Prognosis of stage II and III colon carcinoma treated with adjuvant 5-FU or FOLFIRI in relation to microsatellite status, results of the PETACC-3 trial. Ann Oncol. 2015 Jan;26(1):126-32 2014 Oct 30.
» PubMed
2015 / 10.1172/JCI80454
Sabine A, Bovay E, Demir CS, Kimura W, Jaquet M, Agalarov Y, Zangger N, Scallan JP, Graber W, Gulpinar E, Kwak BR, Mäkinen T, Martinez-Corral I, Ortega S, Delorenzi M, Kiefer F, Davis MJ, Djonov V, Miura N, Petrova TV. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature. J Clin Invest. 2015 Oct 1;125(10):3861-77
» PubMed
2015 / 10.1002/cjp2.17
Paquet ER, Cui J, Davidson D, Pietrosemoli N, Hassan HH, Tsofack SP, Maltais A, Hallett MT, Delorenzi M, Batist G, Aloyz R, Lebel M. A 12-gene signature to distinguish colon cancer patients with better clinical outcome following treatment with 5-fluorouracil or FOLFIRI. Ann Oncol. 2015 Jan;26(1):126-32
» PubMed
2015 / PMID: 25622821.
Kurscheid S, Bady P, Sciuscio D, Samarzija I, Shay T, Vassallo I, van Criekinge W, Daniel RT, van den Bent MJ, Marosi C, Weller M, Mason WP, Domany E, Stupp R, Delorenzi M, Hegi ME. Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma. Genome Biol. 2015 Jan 27;16(1):16.
» PubMed
2015 / 10.1038/nm.3967
Guinney J, Dienstmann R, Wang X, de Reyničs A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov; 21(11):1350-6
» PubMed
2014 / doi: 10.1093/annonc/mdu275. PMID: 25057166.
Missiaglia E, Jacobs B, D'Ario G, F. Di Narzo AF, Soneson C, Eva Budinska E, Popovici V, Vecchione L, Gerster S, Pu Yan P, Roth AD, Dirk D, Bosman F, Delorenzi M, Tejpar S. Distal and proximal colon cancers differ in terms of molecular, pathological and clinical features. Ann Oncol. 2014 Oct;25(10):1995-2001
» PubMed
2014 / doi: 10.1371/journal.pone.0100335. PMID: 24967636
Soneson C, Gerster S, Delorenzi M. Batch effect confounding leads to strong bias in performance estimates obtained by cross-validation. PLoS One 2014, Jun 26.
» PubMed
2014 / doi: 10.1016/j.ccr.2014.05.029. PMID: 25087979.
Tremblay AM, Missiaglia E, Galli GG, Hettmer S, Urcia R, Carrara M, Judson RN, Thway K, Nadal G, Selfe JL, Murray G, Calogero RA, De Bari C, Zammit PS, Delorenzi M, Wagers AJ, Shipley J, Wackerhage H, Camargo FD. The Hippo Transducer YAP1 Transforms Activated Satellite Cells and Is a Potent Effector of Embryonal Rhabdomyosarcoma Formation. Cancer Cell 2014, 26(2):273-87.
» PubMed
2014 / doi: 10.1371/journal.pone.0114530. PMID: 25485970.
Ozdemir BC, Hensel J, Secondini C, Wetterwald A, Schwaninger R, Fleischmann A, Raffelsberger W, Poch O, Delorenzi M, Temanni R, Mills IG, van der Pluijm G, Thalmann GN, Cecchini MG. The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches. PLoS One. 2014 Dec 8;9(12):e114530.
» PubMed
2014 / doi: 10.1242/dmm.013904. PMID 24742783
Belmont PJ, Budinska E, Jiang P, Sinnamon MJ, Coffee E, Roper J, Xie T, Rejto PA, Derkits S, Sansom OJ, Delorenzi M, Tejpar S, Hung KE, Martin ES. Cross-species analysis of genetically engineered mouse models of MAPK driven colorectal cancer identifies hallmarks of human disease. Dis Model Mech. 2014 Jun;7(6):613-23
» PubMed
2014 / doi: 10.1038/nm.3708. PMID: 25344738.
Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C, Fend L, Hannani D, Aymeric L, Ma Y, Niso-Santano M, Kepp O, Schultze JL, Tüting T, Belardelli F, Bracci L, La Sorsa V, Ziccheddu G, Sestili P, Urbani F, Delorenzi M, Lacroix-Triki M, Quidville V, Conforti R, Spano JP, Pusztai L, Poirier-Colame V, Delaloge S, Penault-Llorca F, Ladoire S, Arnould L, Cyrta J, Dessoliers MC, Eggermont A, Bianchi ME, Pittet M, Engblom C, Pfirschke C, Préville X, Uzč G, Schreiber RD, Chow MT, Smyth MJ, Proietti E, André F, Kroemer G, Zitvogel L. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014 Nov;20(11):1301-9.
» PubMed
2014 / doi: 10.1016/j.celrep.2014.08.041. PMID: 25242332
Ragusa S, Cheng J, Ivanov KI, Zangger N, Ceteci F, Bernier-Latmani J, Milatos S, Joseph JM, Tercier S, Bouzourene H, Bosman FT, Letovanec I, Marra G, Gonzalez M, Cammareri P, Sansom OJ, Delorenzi M, Petrova TV. PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnthigh Metastatic Colon Cancer Cells. Cell Rep. 2014 Sep 17
» PubMed
2014 / doi: 10.1182/blood-2014-07-584953. PMID: 25224410
Bossard C, Dobay MP, Parrens M, Lamant L, Missiaglia E, Haioun C, Martin A, Fabiani B, Delarue R, Tournilhac O, Delorenzi M, Gaulard P, de Leval L. Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation between protein and mRNA expression. Blood. 2014 Nov 6;124(19):2983-6.
» PubMed
2014 / doi: 10.1371/journal.pone.0099886. eCollection 2014. PMID: 24940606.
Schou JV, Rossi S, Jensen BV, Nielsen DL, Pfeiffer P, Hřgdall E, Yilmaz M, Tejpar S, Delorenzi M, Kruhřffer M, Johansen JS. miR-345 in Metastatic Colorectal Cancer: A Non-Invasive Biomarker for Clinical Outcome in Non-KRAS Mutant Patients Treated with 3rd Line Cetuximab and Irinotecan. PLoS One 2014, 9(6):e99886.
» PubMed
2014 / doi: 10.1093/jnci/dju247. PMID: 25246611
Di Narzo AF, Tejpar S, Rossi S, Yan P, Popovici V, Wirapati P, Budinska E, Xie T, Estrella H, Pavlicek A, Mao M, Martin E, Scott W, Bosman F, Roth A, Delorenzi M. Test of four Colon Cancer Risk-Scores in FFPE Microarray Gene Expression data. J Natl Cancer Inst. 2014: Sep 22: 106(10).
» PubMed
2013 / 10.1002/path.4212
Budinska E, Popovici V, Tejpar S, D'Ario G, Lapique N, Sikora KO, Di Narzo AF, Yan P, Hodgson JG, Weinrich S, Bosman F, Roth A, Delorenzi M. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J Pathol. 2013 Jul 8
» PubMed
2013 / 10.1186/1471-2105-14-91
Soneson C, Delorenzi M. A comparison of methods for differential expression analysis of RNA-seq data. BMC Bioinformatics 14:91
» PubMed
2012
Rossi S, Di Narzo AF, Mestdagh P, Jacobs B, Bosman FT, Gustavsson B, Majoie B, Roth A, Vandesompele J, Rigoutsos I, Delorenzi M, Tejpar S. microRNAs in colon cancer: a roadmap for discovery. FEBS Lett. 2012 Sep 21;586(19):3000-7
» PubMed
2012 / 10.1111/j.1755-148X.2012.01018.x
Anghel SI, Correa-Rocha R, Budinska E, Boligan KF, Abraham S, Colombetti S, Fontao L, Mariotti A, Rimoldi D, Ghanem GE, Fisher DE, Lévy F, Delorenzi M, Piguet V. Breast cancer suppressor candidate-1 (BCSC-1) is a melanoma tumor suppressor that down regulates MITF. Pigment Cell Melanoma Res. 2012 Jul;25(4):482-7
» PubMed
2012 / 10.1093/neuonc/nos072
Bady P, Diserens AC, Castella V, Kalt S, Heinimann K, Hamou MF, Delorenzi M, Hegi ME. DNA fingerprinting of glioma cell lines and considerations on similarity measurements. Neuro Oncol. 2012 Jun;14(6):701-11
» PubMed
2012 / 10.1007/s00401-012-1016-2
Bady P, Sciuscio D, Diserens AC, Bloch J, van den Bent MJ, Marosi C, Dietrich PY, Weller M, Mariani L, Heppner FL, Mcdonald DR, Lacombe D, Stupp R, Delorenzi M, Hegi ME. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol. 2012 Oct;124(4):547-60
» PubMed
2012 / 10.1038/onc.2011.356
Carrascosa C, Obula RG, Missiaglia E, Lehr HA, Delorenzi M, Frattini M, Rüegg C, Mariotti A. MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells. Oncogene. 2012 Mar 22;31(12):1521-32
» PubMed
2012 / 10.1158/1078-0432.CCR-11-0383
Desmedt C, Majjaj S, Kheddoumi N, Singhal SK, Haibe-Kains B, El Ouriaghli F, Chaboteaux C, Michiels S, Lallemand F, Journe F, Duvillier H, Loi S, Quackenbush J, Dekoninck S, Blanpain C, Lagneaux L, Houhou N, Delorenzi M, Larsimont D, Piccart M, Sotiriou C. Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment. Clin Cancer Res. 2012 Feb 15;18(4):1004-14
» PubMed
2012 / 10.1200/JCO.2011.39.5814
Popovici V, Budinska E, Tejpar S, Weinrich S, Estrella H, Hodgson G, Van Cutsem E, Xie T, Bosman FT, Roth AD, Delorenzi M. Identification of a poor-prognosis BRAF-mutant-like population of patients with colon cancer. J Clin Oncol. 2012 Apr 20;30(12):1288-95
» PubMed
2012 / 10.1093/jnci/djs427
Roth AD, Delorenzi M, Tejpar S, Yan P, Klingbiel D, Fiocca R, d'Ario G, Cisar L, Labianca R, Cunningham D, Nordlinger B, Bosman F, Van Cutsem E. Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer. J Natl Cancer Inst. 2012 Nov 7;104(21):1635-46
» PubMed
2012 / 10.1002/path.4092
Tian S, Roepman P, Popovici V, Michaut M, Majewski I, Salazar R, Santos C, Rosenberg R, Nitsche U, Mesker WE, Bruin S, Tejpar S, Delorenzi M, Bernards R, Simon I. A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency. J Pathol. 2012 Aug 27
» PubMed
2012 / 10.1371/journal.pone.0042001
Xie T, D' Ario G, Lamb JR, Martin E, Wang K, Tejpar S, Delorenzi M, Bosman FT, Roth AD, Yan P, Bougel S, Di Narzo AF, Popovici V, Budinská E, Mao M, Weinrich SL, Rejto PA, Hodgson JG. A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations. PLoS One. 2012;7(7):e42001
» PubMed
2012 / 10.1038/onc.2011.218
Zaric J, Joseph JM, Tercier S, Sengstag T, Ponsonnet L, Delorenzi M, Rüegg C. Identification of MAGI1 as a tumor suppressor protein induced by COX-2 inhibitors in colon cancer cells. Oncogene 2012; 31: 48–59
» PubMed
2011 / 10.1158/1535-7163.MCT-11-0048
Hegi ME, Diserens AC, Bady P, Kamoshima Y, Kouwenhoven MC, Delorenzi M, Lambiv WL, Hamou MF, Matter MS, Koch A, Heppner FL, Yonekawa Y, Merlo A, Frei K, Mariani L, Hofer S. Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib--a phase II trial. Mol Cancer Ther. 2011 Jun;10(6):1102-12
» PubMed
2011 / 10.1371/journal.pone.0018640
Planche A, Bacac M, Provero P, Fusco C, Delorenzi M, Stehle JC, Stamenkovic I. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer. PLoS One. 2011;6(5):e18640
» PubMed
2011 / 10.1093/bioinformatics/btr233
Popovici V, Budinská E, Delorenzi M. Rgtsp: a generalized top scoring pairs package for class prediction. Bioinformatics. 2011 Jun 15;27(12):1729-30
» PubMed
2011 / 10.1093/jnci/djr170
Tejpar S, Saridaki Z, Delorenzi M, Bosman F, Roth AD. Microsatellite instability, prognosis and drug sensitivity of stage II and III colorectal cancer: more complexity to the puzzle. J Natl Cancer Inst. 2011 Jun 8;103(11):841-4
» PubMed
2010 / 10.1016/S1470-2045(10)70130-3
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010 Aug;11(8):753-62
» PubMed
2010 / 10.1186/bcr2468
Popovici V, Chen W, Gallas BG, Hatzis C, Shi W, Samuelson FW, Nikolsky Y, Tsyganova M, Ishkin A, Nikolskaya T, Hess KR, Valero V, Booser D, Delorenzi M, Hortobagyi GN, Shi L, Symmans WF, Pusztai L. Effect of training-sample size and classification difficulty on the accuracy of genomic predictors. Breast Cancer Res. 2010;12(1):R5
» PubMed
2010 / 10.1200/JCO.2009.23.3452
Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010 Jan 20;28(3):466-74
» PubMed
2010 / 10.1634/theoncologist.2009-0233
Tejpar S, Bertagnolli M, Bosman F, Lenz HJ, Garraway L, Waldman F, Warren R, Bild A, Collins-Brennan D, Hahn H, Harkin DP, Kennedy R, Ilyas M, Morreau H, Proutski V, Swanton C, Tomlinson I, Delorenzi M, Fiocca R, Van Cutsem E, Roth A. Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist. 2010;15(4):390-404
» PubMed
2009 / 10.1038/nm.1908
Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, André S, Piccart M, Campone M, Brain E, Macgrogan G, Petit T, Jassem J, Bibeau F, Blot E, Bogaerts J, Aguet M, Bergh J, Iggo R, Delorenzi M. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009 Jan;15(1):68-74
» PubMed
2009 / 10.1083/jcb.200901104
Norrmén C, Ivanov KI, Cheng J, Zangger N, Delorenzi M, Jaquet M, Miura N, Puolakkainen P, Horsley V, Hu J, Augustin HG, Ylä-Herttuala S, Alitalo K, Petrova TV. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. J Cell Biol. 2009 May 4;185(3):439-57
» PubMed
2008 / 10.1186/1471-2164-9-239
Loi S, Haibe-Kains B, Desmedt C, Wirapati P, Lallemand F, Tutt AM, Gillet C, Ellis P, Ryder K, Reid JF, Daidone MG, Pierotti MA, Berns EM, Jansen MP, Foekens JA, Delorenzi M, Bontempi G, Piccart MJ, Sotiriou C. Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics. 2008 May 22;9:239
» PubMed
2008 / 10.1158/0008-5472.CAN-08-0841
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2007
Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G, Delorenzi M, Zhang Y, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris AL, Klijn JG, Foekens JA, Cardoso F, Piccart MJ, Buyse M, Sotiriou C; TRANSBIG Consortium. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007 Jun 1;13(11):3207-14
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2007
Loi S, Haibe-Kains B, Desmedt C, Lallemand F, Tutt AM, Gillet C, Ellis P, Harris A, Bergh J, Foekens JA, Klijn JG, Larsimont D, Buyse M, Bontempi G, Delorenzi M, Piccart MJ, Sotiriou C. Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol. 2007 Apr 1;25(10):1239-46
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2006
Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ; TRANSBIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006 Sep 6;98(17):1183-92
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2006
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