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Gene Review

GAGE1  -  G antigen 1

Homo sapiens

Synonyms: Antigen MZ2-F, CT4.1, Cancer/testis antigen 4.1, GAGE-1
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Disease relevance of GAGE1

  • About 50% of melanoma patients carry on their tumor at least one of the presently defined antigens encoded by the MAGE, BAGE, and GAGE genes [1].
  • The two genes of the GAGE family that code for this peptide, namely GAGE-1 and GAGE-2, are expressed in a significant proportion of melanomas (24%), sarcomas (25%), non-small cell lung cancers (19%), head and neck tumors (19%), and bladder tumors (12%) [1].
  • Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma [2].
  • The GAGE family of antigens may be potential tumor markers of minimal residual disease [2].
  • The absence of GAGE-1 expression in normal brain, its relatively high frequency of expression in high-grade brain tumors, and its unique 3' sequence, suggest it may represent a useful target for specific immunotherapy [3].

Psychiatry related information on GAGE1

  • Spiking Phineas Gage: a neurocomputational theory of cognitive-affective integration in decision making [4].
  • In much contemporary literature the Phineas Gage case is described as contributing to the development of lobotomy and leucotomy but the historical evidence shows this to be an almost completely erroneous view [5].

High impact information on GAGE1

  • These results suggest that a novel subset of CD4(+) T cells may be crucial in the development of pathology during human RSV infection and that genetic or environmental factors prior to or at the time of G antigen exposure may affect the commitment of this discrete antigen-specific T cell subset to Th2 differentiation [6].
  • The repression of tumor-specific G antigens during E2 senescence supports a reversal of the tumorigenic phenotype by E2 and the potential approach of tumor-specific G antigen-specific immunotherapy for cervical cancer [7].
  • GAGE proteins are expressed in a variety of tumors and in testis [8].
  • This gene is located on the human X chromosome, and it is homologous to a family of genes encoding GAGE-like proteins [8].
  • PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus [8].

Biological context of GAGE1

  • Treatment of normal and tumor cultured cells with a demethylating agent, azadeoxycytidine, resulted in the transcriptional activation of GAGE genes, suggesting that their expression in tumors results from a demethylation process [9].
  • These GAGE genes are located in the p11.2-p11.4 region of chromosome X. They are not expressed in normal tissues, except in testis, but a large proportion of tumors of various histological origins express at least one of these genes [9].
  • These novel lineage-unrelated HLA-A3.1-restricted melanoma epitopes do not derive from MAGE, BAGE, or GAGE gene families, as evaluated by the COS-7 transfection assay [10].
  • GAGE and immunocytology were more sensitive than histology or tyrosine hydroxylase reverse transcription-PCR when marrows were obtained from patients on therapy or off therapy during clinical remission [11].
  • PURPOSE: XAGE-1 was originally identified by the search for PAGE/GAGE-related genes using expressed sequence tag database and was shown to exhibit characteristics of cancer/testis-like antigens [12].

Anatomical context of GAGE1

  • Characterization of the GAGE genes that are expressed in various human cancers and in normal testis [9].
  • Human genes expressed exclusively in tumors and male germ line cells, such as those of the MAGE, BAGE, and GAGE families, encode antigens recognized by T lymphocytes, which are potentially useful for antitumor immunotherapy [13].
  • Simultaneous bone marrow and blood samples (85 patients), marrow-only samples (35 patients), and blood-only samples (13 patients) were examined for the presence of GAGE expression using reverse transcription-PCR [14].
  • Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines [15].
  • The model also simulates the historical case of Phineas Gage as well as subsequent patients whose ability to make decisions became impeded by damage to the ventromedial prefrontal cortex [4].

Associations of GAGE1 with chemical compounds

  • (Compositae) the first intermediate in DMSP biosynthesis has been shown to be S-methylmethionine (SMM) (A.D. Hanson, J. Rivoal, L. Paquet, D.A. Gage [1994] Plant Physiol 105: 103-110) [16].
  • In addition, the frequency of expression of more recently discovered tumour antigens (BAGE, GAGE -1, -2 and GAGE -3, -6) was established using RT-PCR and ethidium bromide staining [17].
  • Measurements of acetylcholine-induced single-channel conductance and null potentials at the amphibian motor end-plate in solutions containing Na, K, Li and Cs ions (Gage & Van Helden, 1979; J [18].
  • The Whitney Mercury Strain Gage and a Nonin Cardiopulmonary monitor were used to observe sucking characteristics and cardiopulmonary functions during feeding [19].
  • Following my presentation, James Gage, Editor-in-Chief for Gait and Posture, and David Winter, Associate Editor for review articles requested a manuscript for publication [20].

Other interactions of GAGE1

  • A GenBankTM data base search using the GCG Wisconsin software package revealed the shorter approximately 600-bp transcript (designated GAGE-7) to be a new member of the GAGE family [21].
  • The second approximately 700-bp transcript was a novel gene (designated PAGE-1, "prostate associated gene") with only 45% homology to GAGE gene family members [21].
  • NY-TLU-57, GAGE1, SAGE1 were expressed more frequently in tumor samples than in healthy tissues [22].
  • Therefore, the RT-PCR assays for GAGE-1, -2 and MDM2 might be useful adjuncts in cytodiagnosis of liver neoplasms [23].
  • GAGE-1, -2, and -8 form one subset, almost identical among themselves, while GAGE-3 to -7 constitute the other subset [24].

Analytical, diagnostic and therapeutic context of GAGE1

  • Sequence alignment showed that an additional exon, which is present only in the mRNA of GAGE-1, has been disrupted in gene GAGE-7B by the insertion of a long interspersed repeated element retroposon [9].
  • There was evidence of response by immunocytology (six of nine), by GAGE RT-PCR (seven of 12), and by (131)I-3F8 scans (six of six) [25].
  • Association between molecular detection of GAGE and survival in patients with malignant melanoma: a retrospective cohort study [14].
  • Intraperitoneal or intramuscular injection of G antigen conferred protection to mice and was associated with the induction of high titers of neutralizing antibodies [26].
  • Sequence analysis of gene 9, encoding the G antigen, showed that Argentine strains cluster with most G9 isolates from other countries, showing less than 2% nucleotide divergence among them, but are distinctive from them in that they present some unique amino acid changes [27].


  1. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. Van den Eynde, B., Peeters, O., De Backer, O., Gaugler, B., Lucas, S., Boon, T. J. Exp. Med. (1995) [Pubmed]
  2. Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma. Cheung, I.Y., Cheung, N.K. Clin. Cancer Res. (1997) [Pubmed]
  3. Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers. Scarcella, D.L., Chow, C.W., Gonzales, M.F., Economou, C., Brasseur, F., Ashley, D.M. Clin. Cancer Res. (1999) [Pubmed]
  4. Spiking Phineas Gage: a neurocomputational theory of cognitive-affective integration in decision making. Wagar, B.M., Thagard, P. Psychological review. (2004) [Pubmed]
  5. Phineas Gage's contribution to brain surgery. Macmillan, M. Journal of the history of the neurosciences. (1996) [Pubmed]
  6. Immunopathology in RSV infection is mediated by a discrete oligoclonal subset of antigen-specific CD4(+) T cells. Varga, S.M., Wang, X., Welsh, R.M., Braciale, T.J. Immunity (2001) [Pubmed]
  7. Transcriptome signature of irreversible senescence in human papillomavirus-positive cervical cancer cells. Wells, S.I., Aronow, B.J., Wise, T.M., Williams, S.S., Couget, J.A., Howley, P.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus. Brinkmann, U., Vasmatzis, G., Lee, B., Yerushalmi, N., Essand, M., Pastan, I. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Characterization of the GAGE genes that are expressed in various human cancers and in normal testis. De Backer, O., Arden, K.C., Boretti, M., Vantomme, V., De Smet, C., Czekay, S., Viars, C.S., De Plaen, E., Brasseur, F., Chomez, P., Van den Eynde, B., Boon, T., van der Bruggen, P. Cancer Res. (1999) [Pubmed]
  10. Multiple melanoma-associated epitopes recognized by HLA-A3-restricted CTLs and shared by melanomas but not melanocytes. Mazzocchi, A., Storkus, W.J., Traversari, C., Tarsini, P., Maeurer, M.J., Rivoltini, L., Vegetti, C., Belli, F., Anichini, A., Parmiani, G., Castelli, C. J. Immunol. (1996) [Pubmed]
  11. Detection of microscopic neuroblastoma in marrow by histology, immunocytology, and reverse transcription-PCR of multiple molecular markers. Cheung, I.Y., Barber, D., Cheung, N.K. Clin. Cancer Res. (1998) [Pubmed]
  12. XAGE-1 expression in non-small cell lung cancer and antibody response in patients. Nakagawa, K., Noguchi, Y., Uenaka, A., Sato, S., Okumura, H., Tanaka, M., Shimono, M., Ali Eldib, A.M., Ono, T., Ohara, N., Yoshino, T., Yamashita, K., Tsunoda, T., Aoe, M., Shimizu, N., Nakayama, E. Clin. Cancer Res. (2005) [Pubmed]
  13. Identification of a new MAGE gene with tumor-specific expression by representational difference analysis. Lucas, S., De Smet, C., Arden, K.C., Viars, C.S., Lethé, B., Lurquin, C., Boon, T. Cancer Res. (1998) [Pubmed]
  14. Association between molecular detection of GAGE and survival in patients with malignant melanoma: a retrospective cohort study. Cheung, I.Y., Cheung, N.K., Ghossein, R.A., Satagopan, J.M., Bhattacharya, S., Coit, D.G. Clin. Cancer Res. (1999) [Pubmed]
  15. Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines. Duan, Z., Duan, Y., Lamendola, D.E., Yusuf, R.Z., Naeem, R., Penson, R.T., Seiden, M.V. Clin. Cancer Res. (2003) [Pubmed]
  16. Evidence implicating dimethylsulfoniopropionaldehyde as an intermediate in dimethylsulfoniopropionate biosynthesis. James, F., Paquet, L., Sparace, S.A., Gage, D.A., Hanson, A.D. Plant Physiol. (1995) [Pubmed]
  17. MAGE, BAGE and GAGE: tumour antigen expression in benign and malignant ovarian tissue. Gillespie, A.M., Rodgers, S., Wilson, A.P., Tidy, J., Rees, R.C., Coleman, R.E., Murray, A.K. Br. J. Cancer (1998) [Pubmed]
  18. Cation permeation of the amphibian motor end-plate. Barry, P.H., Gage, P.W., Van Helden, D.F. J. Membr. Biol. (1979) [Pubmed]
  19. Oral support measures used in feeding the preterm infant. Hill, A.S., Kurkowski, T.B., Garcia, J. Nursing research. (2000) [Pubmed]
  20. The evolution of clinical gait analysis part l: kinesiological EMG. Sutherland, D.H. Gait & posture. (2001) [Pubmed]
  21. Isolation and characterization of PAGE-1 and GAGE-7. New genes expressed in the LNCaP prostate cancer progression model that share homology with melanoma-associated antigens. Chen, M.E., Lin, S.H., Chung, L.W., Sikes, R.A. J. Biol. Chem. (1998) [Pubmed]
  22. Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma. Atanackovic, D., Blum, I., Cao, Y., Wenzel, S., Bartels, K., Faltz, C., Hossfeld, D.K., Hegewisch-Becker, S., Bokemeyer, C., Leuwer, R. Cancer Biol. Ther. (2006) [Pubmed]
  23. Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia. Schlott, T., Ahrens, K., Ruschenburg, I., Reimer, S., Hartmann, H., Droese, M. Br. J. Cancer (1999) [Pubmed]
  24. Minimal residual disease in neuroblastoma: to GAGE or not to GAGE. Oltra, S., Martínez, F., Orellana, C., Grau, E., Fernández, J.M., Cañete, A., Castel, V. Oncol. Res. (2004) [Pubmed]
  25. Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. Cheung, N.K., Kushner, B.H., Cheung, I.Y., Kramer, K., Canete, A., Gerald, W., Bonilla, M.A., Finn, R., Yeh, S.J., Larson, S.M. J. Clin. Oncol. (1998) [Pubmed]
  26. Immunogenic and protective properties of rabies virus glycoprotein expressed by baculovirus vectors. Prehaud, C., Takehara, K., Flamand, A., Bishop, D.H. Virology (1989) [Pubmed]
  27. Emergence of G9 P[6] human rotaviruses in Argentina: phylogenetic relationships among G9 strains. Bok, K., Palacios, G., Sijvarger, K., Matson, D., Gomez, J. J. Clin. Microbiol. (2001) [Pubmed]
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