DOI QR코드

DOI QR Code

Expression of Cancer-Testis Genes in Brain Tumors

  • Lee, Myoung-Hee (Departments of Neurosurgery, Keimyung University School of Medicine) ;
  • Son, Eun-Ik (Departments of Neurosurgery, Keimyung University School of Medicine) ;
  • Kim, Ealmaan (Departments of Neurosurgery, Keimyung University School of Medicine) ;
  • Kim, In-Soo (Departments of Neurosurgery, Keimyung University School of Medicine) ;
  • Yim, Man-Bin (Departments of Neurosurgery, Keimyung University School of Medicine) ;
  • Kim, Sang-Pyo (Departments of Pathology, Keimyung University School of Medicine)
  • Published : 2008.04.28

Abstract

Objective : Cancer-testis (CT) genes are considered promising candidates for immunotherapeutic approaches. The aim of this study was to investigate which CT genes should be targeted in immunotherapy for brain tumors. Methods : We investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4, and HOMTES-85) using reverse-transcription polymerase chain reaction in 26 meningiomas and 32 other various brain tumor specimens, obtained from the patients during tumor surgery from 2000 to 2005. Results : The most frequently expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%) meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2 (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6. Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1 (2/6 or 33%). Conclusion : The data presented here suggest that MAGE-E1 and SOX-6 genes are expressed in a high percentage of human central nervous system tumors, which implies the CT genes could be the potential targets of immunotherapy for human central nervous system tumors.

Keywords

References

  1. Boel P, Wildmann C, Sensi ML, Brasseur R, Renauld JC, Coulie P, et al : BAGE : a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2 : 167-175, 1995 https://doi.org/10.1016/S1074-7613(95)80053-0
  2. Boon T, van der Bruggen P : Human tumor antigens recognized by T lymphocytes. J Exp Med 183 : 725-729, 1996 https://doi.org/10.1084/jem.183.3.725
  3. Brinkmann U, Vasmatzis G, Lee B, Pastan I : Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database. Cancer Res 59 : 1445-1448, 1999
  4. Chen YT, Scanlan MJ, Sahin U, Türeci O, Gure AO, Tsang S, et al : A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A 94 : 1914-1918, 1997
  5. Chen YT, Scanlan MJ, Venditti CA, Chua R, Theiler G, Stevenson BJ, et al : Identification of cancer/testis-antigen genes by massively parallel signature sequencing. Proc Natl Acad Sci U S A 102 : 7940- 7945, 2005
  6. Feller AJ, Duan Z, Penson R, Toh HC, Seiden MV : TRAG-3, a novel cancer/testis antigen, is overexpressed in the majority of melanoma cell lines and malignant melanoma. Anticancer Res 20 : 4147-4151, 2000
  7. Goodyear O, Piper K, Khan N, Starczynski J, Mahendra P, Pratt G, et al : CD8+ T cells specific for cancer germline gene antigens are found in many patients with multiple myeloma, and their frequency correlates with disease burden. Blood 106 : 4217-4224, 2005 https://doi.org/10.1182/blood-2005-02-0563
  8. Gure AO, Türeci O, Sahin U, Tsang S, Scanlan MJ, Jäger E, et al : SSX : a multigene family with several members transcribed in normal testis and human cancer. Int J Cancer 72 : 965-971, 1997 https://doi.org/10.1002/(SICI)1097-0215(19970917)72:6<965::AID-IJC8>3.0.CO;2-N
  9. Gure AO, Wei IJ, Old LJ, Chen YT : The SSX gene family : characterization of 9 complete genes. Int J Cancer 101 : 448-453, 2002 https://doi.org/10.1002/ijc.10634
  10. Jager D, Unkelbach M, Frei C, Bert F, Scanlan MJ, Jager E, et al : Identification of tumor-restricted antigens NY-BR-1, SCP-1, and a new cancer/testis-like antigen NW-BR-3 by serological screening of a testicular library with breast cancer serum. Cancer Immun 2 : 5, 2002
  11. Korangy F, Ormandy LA, Bleck JS, Klempnauer J, Wilkens L, Manns MP, et al : Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma. Clin Cancer Res 10 : 4332-4341, 2004 https://doi.org/10.1158/1078-0432.CCR-04-0181
  12. Lethe B, Lucas S, Michaux L, De Smet C, Godelaine D, Serrano A, et al : LAGE-1, a new gene with tumor specificity. Int J Cancer 76 : 903-908, 1998 https://doi.org/10.1002/(SICI)1097-0215(19980610)76:6<903::AID-IJC22>3.0.CO;2-1
  13. Monji M, Nakatsura T, Senju S, Yoshitake Y, Sawatsubashi M, Shinohara M, et al : Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses. Clin Cancer Res 10 : 6047-6057, 2004 https://doi.org/10.1158/1078-0432.CCR-04-0475
  14. Ono T, Kurashige T, Harada N, Noguchi Y, Saika T, Niikawa N, et al : Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci U S A 98 : 3282-3287, 2001
  15. Sahin U, Koslowski M, Tureci O, Eberle T, Zwick C, Romeike B, et al : Expression of cancer testis genes in human brain tumors. Clin Cancer Res 6 : 3916-3922, 2000
  16. Sasaki M, Nakahira K, Kawano Y, Katakura H, Yoshimine T, Shimizu K, et al : MAGE-E1, a new member of the melanomaassociated antigen gene family and its expression in human glioma. Cancer Res 61 : 4809-4814, 2001
  17. Scanlan MJ, Gordon CM, Williamson B, Lee SY, Chen YT, Stockert E, et al : Identification of cancer/testis genes by database mining and mRNA expression analysis. Int J Cancer 98 : 485-492, 2002 https://doi.org/10.1002/ijc.10276
  18. Scanlan MJ, Simpson AJ, Old LJ : The cancer/testis genes : review, standardization, and commentary. Cancer Immun 4 : 1, 2004
  19. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ : Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5 : 615-625, 2005 https://doi.org/10.1038/nrc1669
  20. Tureci O, Sahin U, Schobert I, Koslowski M, Scmitt H, Schild HJ, et al : The SSX-2 gene, which is involved in the t (X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOMMEL- 40. Cancer Res 56 : 4766-4772, 1996
  21. Tureci O, Sahin U, Zwick C, Koslowski M, Seitz G, Pfreundschuh M : Identification of a meiosis-specific protein as a member of the class of cancer/testis antigens. Proc Natl Acad Sci U S A 95 : 5211-5216, 1998
  22. Ueda R, Iizuka Y, Yoshida K, Kawase T, Kawakami Y, Toda M : Identification of a human glioma antigen, SOX6, recognized by patients' sera. Oncogene 23 : 1420-1427, 2004 https://doi.org/10.1038/sj.onc.1207252
  23. Ueda R, Yoshida K, Kawakami Y, Kawase T, Toda M : Immunohistochemical analysis of SOX6 expression in human brain tumors. Brain Tumor Pathol 21 : 117-120, 2004 https://doi.org/10.1007/BF02482186
  24. van Baren N, Bonnet MC, Dreno B, Khammari A, Dorval T, Piperno-Neumann S, et al : Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. J Clin Oncol 23 : 9008-9021, 2005 https://doi.org/10.1200/JCO.2005.08.375
  25. van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T : A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 182 : 689-698, 1995 https://doi.org/10.1084/jem.182.3.689
  26. Wang Z, Zhang Y, Mandal A, Zhang J, Giles FJ, Herr JC, et al : The spermatozoa protein, SLLP1, is a novel cancer-testis antigen in hematologic malignancies. Clin Cancer Res 10 : 6544-6550, 2004 https://doi.org/10.1158/1078-0432.CCR-04-0911
  27. Zendman AJ, Cornelissen IM, Weidle UH, Ruiter DJ, van Muijen GN : CTp11, a novel member of the family of human cancer/testis antigens. Cancer Res 59 : 6223-6229, 1999
  28. Zendman AJ, Ruiter DJ, Van Muijen GN : Cancer/testis-associated genes : identification, expression profile, and putative function. J Cell Physiol 194 : 272-288, 2003 https://doi.org/10.1002/jcp.10215

Cited by

  1. The evolutionary history of the SSX family of human C/T-antigens vol.43, pp.6, 2009, https://doi.org/10.1134/s0026893309060065
  2. Rapid evolution and copy number variation of primate RHOXF2 , an X-linked homeobox gene involved in male reproduction and possibly brain function vol.11, pp.None, 2011, https://doi.org/10.1186/1471-2148-11-298
  3. Expression of cancer-testis genes in brain tumors: implications for cancer immunotherapy vol.4, pp.1, 2012, https://doi.org/10.2217/imt.11.145
  4. Downstream and Intermediate Interactions of Synovial Sarcoma-Associated Fusion Oncoproteins and Their Implication for Targeted Therapy vol.2012, pp.None, 2008, https://doi.org/10.1155/2012/249219
  5. Induction of antigen-specific cytotoxic T-cell response by dendritic cells generated from ecto-mesenchymal stem cells infected with an adenovirus containing the MAGE-D4a gene vol.11, pp.4, 2008, https://doi.org/10.3892/ol.2016.4306
  6. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability vol.17, pp.6, 2016, https://doi.org/10.3390/ijms17060890
  7. Identification of HMG-box family establishes the significance of SOX6 in the malignant progression of glioblastoma vol.12, pp.9, 2008, https://doi.org/10.18632/aging.103127
  8. Proteogenomic discovery of neoantigens facilitates personalized multi-antigen targeted T cell immunotherapy for brain tumors vol.12, pp.1, 2008, https://doi.org/10.1038/s41467-021-26936-y