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  • Oncogenomics
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Gene expression profiling defines molecular subtypes of classical Hodgkin's disease

Oncogene volume 21, pages 3095–3102 (2002)Cite this article

Abstract

Although the prognosis of Hodgkin's disease is relatively good, around 20% of patients do not benefit from current therapies and succumb to their disease. A large-scale molecular characterization of disease might help improve HD management. Using cDNA arrays, we studied the mRNA expression levels of ∼1000 selected genes in 34 benign and malignant lymphoid samples including 21 classical Hodgkin's disease (HD) tissue samples. Hierarchical clustering identified three main molecular groups of HD tumours relevant with respect to histology and clinical outcome (response to therapy and survival). Samples from all bad outcome HD (BOHD) patients clustered in one group whereas the two other groups contained most good outcome HD (GOHD) cases. The nodular sclerosis GOHD samples overexpressed genes involved in apoptotic induction and cell signalling, including cytokines, while the BOHD samples were characterized by the upregulation of genes involved in fibroblast activation, angiogenesis, extracellular matrix remodelling, cell proliferation, and the downregulation of tumour suppressor genes. Our results establish a molecular taxonomy of HD correlating with response to therapy and clinical outcome, thereby suggesting the possibility of improving the current prognostic classification.

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References

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM . 2000 Nature 403: 503–511

  • Alizadeh AA, Ross DT, Perou CM, van De Rijn M . 2001 J. Pathol. 195: 41–52

  • Alizadeh AA, Staudt LM . 2000 Curr. Opin. Immunol. 12: 219–225

  • Bartlett NL, Arackal SM . 2000 Curr. Oncol. Rep. 2: 163–171

  • Bertucci F, Houlgatte R, Benziane A, Granjeaud S, Adelaide J, Tagett R, Loriod B, Jacquemier J, Viens P, Jordan B, Birnbaum D, Nguyen C . 2000 Hum. Mol. Genet. 9: 2981–2991

  • Bertucci F, Van Hulst S, Bernard K, Loriod B, Granjeaud S, Tagett R, Starkey M, Nguyen C, Jordan B, Birnbaum D . 1999 Oncogene 18: 3905–3912

  • Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben-Dor A, Sampas N, Dougherty E, Wang E, Marincola F, Gooden C, Lueders J, Glatfelter A, Pollock P, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D, Sondak V . 2000 Nature 406: 536–540

  • Brice P, Bastion Y, Divine M, Nedellec G, Ferrant A, Gabarre J, Reman O, Lepage E, Ferme C . 1996 Cancer 78: 1293–1299

  • Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA . 1992 N. Engl. J. Med. 327: 1478–1484

  • Chan WC . 2001 Hematol. Oncol. 19: 1–17

  • Chen H, Lee JM, Zong Y, Borowitz M, Ng MH, Ambinder RF, Hayward SD . 2001 J. Virol. 75: 2929–2937

  • Cossman J . 2001 J. Histochem. Cytochem. 49: 799–800

  • Cossman J, Annunziata CM, Barash S, Staudt L, Dillon P, He WW, Ricciardi-Castagnoli P, Rosen CA, Carter KC . 1999 Blood 94: 411–416

  • Cossman J, Messineo C, Bagg A . 1998 Lab. Invest. 78: 229–235

  • Dahia PL, Aguiar RC, Alberta J, Kum JB, Caron S, Sill H, Marsh DJ, Ritz J, Freedman A, Stiles C, Eng C . 1999 Hum. Mol. Genet. 8: 185–193

  • Dales JP, Plumas J, Palmerini F, Devilard E, Defrance T, Lajmanovich A, Pradel V, Birg F, Xerri L . 2001 Mol. Pathol. 54: 17–23

  • Drexler HG . 1993 Leuk. Lymphoma 9: 1–25

  • Eisen MB, Spellman PT, Brown PO, Botstein D . 1998 Proc. Natl. Acad. Sci. USA 95: 14863–14868

  • Engels IH, Stepczynska A, Stroh C, Lauber K, Berg C, Schwenzer R, Wajant H, Janicke RU, Porter AG, Belka C, Gregor M, Schulze-Osthoff K, Wesselborg S . 2000 Oncogene 19: 4563–4573

  • Friesen C, Herr I, Krammer PH, Debatin KM . 1996 Nat. Med. 2: 574–577

  • Ge NL, Rudikoff S . 2000 Oncogene 19: 4091–4095

  • Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES . 1999 Science 286: 531–537

  • Granjeaud S, Bertucci F, Jordan BR . 1999 Bioessays 21: 781–790

  • Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC . 1994 Blood 84: 1361–1392

  • Hasenclever D, Diehl V . 1998 N. Engl. J. Med. 339: 1506–1514

  • Hinz M, Loser P, Mathas S, Krappmann D, Dorken B, Scheidereit C . 2001 Blood 97: 2798–2807

  • Hyun T, Yam A, Pece S, Xie X, Zhang J, Miki T, Gutkind JS, Li W . 2000 Blood 96: 3560–3568

  • Izban KF, Ergin M, Huang Q, Qin JZ, Martinez RL, Schnitzer B, Ni H, Nickoloff BJ, Alkan S . 2001 Mod. Pathol. 14: 297–310

  • Kapp U, Yeh WC, Patterson B, Elia AJ, Kagi D, Ho A, Hessel A, Tipsword M, Williams A, Mirtsos C, Itie A, Moyle M, Mak TW . 1999 J. Exp. Med. 189: 1939–1946

  • Kennedy BJ, Fremgen AM, Menck HR . 1998 Cancer 83: 1041–1047

  • Khan J, Wei JS, Ringner M, Saal LH, Ladanyi M, Westermann F, Berthold F, Schwab M, Atnonescu CR, Peterson C, Meltzer PS . 2001 Nat. Med. 7: 673–679

  • Li H, Yuan J . 1999 Curr. Opin. Cell. Biol. 11: 261–266

  • Li S, Ross DT, Kadin ME, Brown PO, Wasik MA . 2001 Am. J. Pathol. 158: 1231–1237

  • Lohri A, Barnett M, Fairey RN, O'Reilly SE, Phillips GL, Reece D, Voss N, Connors JM . 1991 Blood 77: 2292–2298

  • Messineo C, Jamerson MH, Hunter E, Braziel R, Bagg A, Irving SG, Cossman J . 1998 Blood 91: 2443–2451

  • Morente MM, Piris MA, Abraira V, Acevedo A, Aguilera B, Bellas C, Fraga M, Garcia-Del-Moral R, Gomez-Marcos F, Menarguez J, Oliva H, Sanchez-Beato M, Montalban C . 1997 Blood 90: 2429–2436

  • Oya M, Ohtsubo M, Takayanagi A, Tachibana M, Shimizu N, Murai M . 2001 Oncogene 20: 3888–3896

  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D . 2000 Nature 406: 747–752

  • Pianetti S, Arsura M, Romieu-Mourez R, Coffey RJ, Sonenshein GE . 2001 Oncogene 20: 1287–1299

  • Poppema S, Van Den Berg A . 2000 Lab. Invest. 78: 229–235

  • Prolla TA . 1998 Curr. Opin. Cell Biol. 10: 311–316

  • Shaffer AL, Rosenwald A, Hurt EM, Giltnane JM, Lam LT, Pickeral OK, Staudt LM . 2001 Immunity 15: 375–385

  • Staudt LM . 2000 J. Exp. Med. 191: 207–212

  • Stein B, Brady H, Yang MX, Young DB, Barbosa MS . 1996 J. Biol. Chem. 271: 11427–11433

  • The Chipping Forecast. 1999 Nat. Genet. 21: Supplement 1–60

  • Theil J, Laumen H, Marafioti T, Hummel M, Lenz G, Wirth T, Stein H . 2001 Blood 97: 3191–3196

  • Theillet C, Adelaide J, Louason G, Bonnet-Dorion F, Jacquemier J, Adnane J, Longy M, Katsaros D, Sismondi P, Gaudray P, Birnbaum D . 1993 Genes Chromosomes Cancer 7: 219–226

  • Virtaneva K, Wright FA, Tanner SM, Yuan B, Lemon WJ, Caligiuri MA, Bloomfield CD, de La Chapelle AA, Krahe R . 2001 Proc. Natl. Acad. Sci. USA 98: 1124–1129

  • Wakkach A, Cottrez F, Groux H . 2000 Eur. Cytokine Netw. 11: 153–160

  • Warzocha K, Bienvenu J, Ribeiro P, Moullet I, Dumontet C, Neidhardt-Berard EM, Coiffier B, Salles G . 1998 Br. J. Cancer 77: 2357–2362

  • Wellmann A, Thieblemont C, Pittaluga S, Sakai A, Jaffe ES, Siebert P, Raffeld M . 2000 Blood 96: 398–404

  • Xerri L, Bouabdallah R, Camerlo J, Hassoun J . 1994 Hum. Pathol. 25: 449–454

  • Xerri L, Palmerini F, Devilard E, Defrance T, Bouabdallah R, Hassoun J, Birg F . 2000 J. Pathol. 192: 194–202

  • Zhou BP, Hu MC, Miller SA, Yu Z, Xia W, Lin SY, Hung MC . 2000 J. Biol. Chem. 275: 8027–8031

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Acknowledgements

We thank D Maraninchi and C Mawas for their constant support. This work was supported by INSERM, CNRS, Institut Paoli-Calmettes, Génopôle Santé Toulouse and grants 4215 and 4233 from the ‘Association pour la Recherche sur le Cancer’.

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Author notes

  1. Elisabeth Devilard and François Bertucci: E Devilard and F Bertucci contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, Institut Paoli-Calmettes, Marseille, France

    Elisabeth Devilard & Luc Xerri

  2. TAGC, Institut Paoli-Calmettes, Marseille, France

    François Bertucci, Béatrice Loriod, Aurélia Giaconia, Samuel Granjeaud, Catherine Nguyen, Daniel Birnbaum & Remi Houlgatte

  3. CHU Purpan, Toulouse, France

    Pascal Trempat & Pierre Brousset

  4. Department of Haematology, Institut Paoli-Calmettes, Marseille, France

    Reda Bouabdallah

  5. INSERM U119, Institut Paoli-Calmettes, IFR 57 and Université de la Méditerranée, Marseille, France

    Daniel Birnbaum, Françoise Birg & Luc Xerri

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  1. Elisabeth Devilard
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  2. François Bertucci
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Correspondence to Luc Xerri.

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Devilard, E., Bertucci, F., Trempat, P. et al. Gene expression profiling defines molecular subtypes of classical Hodgkin's disease. Oncogene 21, 3095–3102 (2002). https://doi.org/10.1038/sj.onc.1205418

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