Frequent MAGE Mutations in Human Melanoma

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Sep 24

PMID 20862285

Citations 17

Authors

Otavia L Caballero

Qi Zhao

Donata Rimoldi

Brian J Stevenson

Suzanne Svobodova

Sylvie Devalle

Ute F Rohrig

Anna Pagotto

Olivier Michielin

Daniel Speiser

Jedd D Wolchok

Cailian Liu

Tanja Pejovic

Kunle Odunsi

Francis Brasseur

Benoit J Van den Eynde

Lloyd J Old

Xin Lu

Jonathan Cebon

Robert L Strausberg

Andrew J Simpson

Affiliations

Soon will be listed here.

Abstract

Background: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype.

Methodology/principal Findings: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1.

Significance: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.

Citing Articles

Melanoma Antigen Family A (MAGE A) as Promising Biomarkers and Therapeutic Targets in Bladder Cancer.

Verma S, Swain D, Kushwaha P, Brahmbhatt S, Gupta K, Sundi D Cancers (Basel). 2024; 16(2).

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X-chromosome variants are associated with aldosterone producing adenomas.

Dutta R, Larsson M, Arnesen T, Heie A, Walz M, Alesina P Sci Rep. 2021; 11(1):10562.

PMID: 34006971 PMC: 8131628. DOI: 10.1038/s41598-021-89986-8.

MAGE-Targeted Gold Nanoparticles for Ultrasound Imaging-Guided Phototherapy in Melanoma.

Li X, Zhong S, Zhang C, Li P, Ran H, Wang Z Biomed Res Int. 2020; 2020:6863231.

PMID: 33015175 PMC: 7519981. DOI: 10.1155/2020/6863231.

Differential expression of MAGEA6 toggles autophagy to promote pancreatic cancer progression.

Tsang Y, Wang Y, Kong K, Grzeskowiak C, Zagorodna O, Dogruluk T Elife. 2020; 9.

PMID: 32270762 PMC: 7164953. DOI: 10.7554/eLife.48963.

T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.

Neubert N, Schmittnaegel M, Bordry N, Nassiri S, Wald N, Martignier C Sci Transl Med. 2018; 10(436).

PMID: 29643229 PMC: 5957531. DOI: 10.1126/scitranslmed.aan3311.

References

Sharma P, Shen Y, Wen S, Bajorin D, Reuter V, Old L . Cancer-testis antigens: expression and correlation with survival in human urothelial carcinoma. Clin Cancer Res. 2006; 12(18):5442-7. DOI: 10.1158/1078-0432.CCR-06-0527. View

Simpson A, Caballero O, Jungbluth A, Chen Y, Old L . Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005; 5(8):615-25. DOI: 10.1038/nrc1669. View

Pleasance E, Cheetham R, Stephens P, McBride D, Humphray S, Greenman C . A comprehensive catalogue of somatic mutations from a human cancer genome. Nature. 2009; 463(7278):191-6. PMC: 3145108. DOI: 10.1038/nature08658. View

Monte M, Simonatto M, Peche L, Bublik D, Gobessi S, Pierotti M . MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents. Proc Natl Acad Sci U S A. 2006; 103(30):11160-5. PMC: 1544058. DOI: 10.1073/pnas.0510834103. View

Brichard V, Lejeune D . Cancer immunotherapy targeting tumour-specific antigens: towards a new therapy for minimal residual disease. Expert Opin Biol Ther. 2008; 8(7):951-68. DOI: 10.1517/14712598.8.7.951. View

Gure A, Chua R, Williamson B, Gonen M, Ferrera C, Gnjatic S . Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res. 2005; 11(22):8055-62. DOI: 10.1158/1078-0432.CCR-05-1203. View

Jeon C, Shin I, Park J, Chae H . Prognostic significance of MAGE in peritoneal washes in gastric carcinoma patients without peritoneal metastasis: results of a 5-year follow-up study. J Clin Gastroenterol. 2010; 44(10):682-6. DOI: 10.1097/MCG.0b013e3181d6bb0b. View

Yang B, OHerrin S, Wu J, Reagan-Shaw S, Ma Y, Bhat K . MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res. 2007; 67(20):9954-62. DOI: 10.1158/0008-5472.CAN-07-1478. View

Jones S, Zhang X, Parsons D, Cheng-Ho Lin J, Leary R, Angenendt P . Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008; 321(5897):1801-6. PMC: 2848990. DOI: 10.1126/science.1164368. View

10.

Grau E, Oltra S, Martinez F, Orellana C, Canete A, Fernandez J . MAGE-A1 expression is associated with good prognosis in neuroblastoma tumors. J Cancer Res Clin Oncol. 2008; 135(4):523-31. DOI: 10.1007/s00432-008-0484-1. View

11.

Singer G, Stohr R, Cope L, Dehari R, Hartmann A, Cao D . Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am J Surg Pathol. 2005; 29(2):218-24. DOI: 10.1097/01.pas.0000146025.91953.8d. View

12.

Atanackovic D, Hildebrandt Y, Jadczak A, Cao Y, Luetkens T, Meyer S . Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells. Haematologica. 2009; 95(5):785-93. PMC: 2864385. DOI: 10.3324/haematol.2009.014464. View

13.

Bergeron A, Picard V, LaRue H, Harel F, Hovington H, Lacombe L . High frequency of MAGE-A4 and MAGE-A9 expression in high-risk bladder cancer. Int J Cancer. 2009; 125(6):1365-71. DOI: 10.1002/ijc.24503. View

14.

Liu W, Cheng S, Asa S, Ezzat S . The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. Cancer Res. 2008; 68(19):8104-12. DOI: 10.1158/0008-5472.CAN-08-2132. View

15.

Peikert T, Specks U, Farver C, Erzurum S, Comhair S . Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis. Cancer Res. 2006; 66(9):4693-700. DOI: 10.1158/0008-5472.CAN-05-3327. View

16.

Atanackovic D, Luetkens T, Hildebrandt Y, Arfsten J, Bartels K, Horn C . Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma. Clin Cancer Res. 2009; 15(4):1343-52. DOI: 10.1158/1078-0432.CCR-08-0989. View

17.

De Plaen E, Arden K, Traversari C, Gaforio J, Szikora J, De Smet C . Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics. 1994; 40(5):360-9. DOI: 10.1007/BF01246677. View

18.

Parsons D, Jones S, Zhang X, Cheng-Ho Lin J, Leary R, Angenendt P . An integrated genomic analysis of human glioblastoma multiforme. Science. 2008; 321(5897):1807-12. PMC: 2820389. DOI: 10.1126/science.1164382. View

19.

Pejovic T, Pande N, Mori M, Mhawech-Fauceglia P, Harrington C, Mongoue-Tchokote S . Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes. Transl Oncol. 2009; 2(4):341-9. PMC: 2781076. DOI: 10.1593/tlo.09199. View

20.

Guerois R, Nielsen J, Serrano L . Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J Mol Biol. 2002; 320(2):369-87. DOI: 10.1016/S0022-2836(02)00442-4. View