| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Institute of Biochemistry,* RWTH-Aachen, Aachen; the Institute of Pathology, University of Regensburg Medical School, Regensburg; and Institute of Pathology, University Hospital Bonn, Bonn, Germany
Homozygous deletions of human chromosomal region 9p21 occur frequently in malignant melanoma and are associated with the loss of the tumor suppressor genes p16(INK4a) and p15(INK4b). In the same chromosomal region the methylthioadenosine phosphorylase (MTAP) gene is localized and therefore may also serve as a tumor suppressor gene. The aim of this study was to analyze MTAP mutations and expression patterns in malignant melanomas. To examine the MTAP gene and expression of MTAP protein we screened 9 human melanoma cell lines and primary human melanocytes by reverse transcriptase-polymerase chain reaction, sequencing, and immunoblotting. Analyzing the melanoma cell lines we found significant down-regulation of MTAP mRNA expression. In only one cell line, HTZ19d, this was due to homozygous deletion of exon 2 to 8 whereas in the other cell lines promoter hypermethylation was detected. MTAP expression was further analyzed in vivo by immunohistochemical staining of 38 tissue samples of benign melanocytic nevi, melanomas, and melanoma metastases. In summary, we demonstrate significant inverse correlation between MTAP protein expression and progression of melanocytic tumors as the amount of MTAP protein staining decreases from benign melanocytic nevi to metastatic melanomas. Our results suggest an important role of MTAP inactivation in the development of melanomas. This finding may be of great clinical significance because recently an association between MTAP activity and interferon sensitivity has been suggested.
This article has been cited by other articles:
 |
|
 |
|
  H.-Y. Huang, S.-H. Li, S.-C. Yu, F.-F. Chou, C.-C. Tzeng, T.-H. Hu, Y.-H. Uen, Y.-F. Tian, Y.-H. Wang, F.-M. Fang, et al. Homozygous Deletion of MTAP Gene as a Poor Prognosticator in Gastrointestinal Stromal Tumors Clin. Cancer Res., November 15, 2009; 15(22): 6963 - 6972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Dorshorst and C. M. Ashwell Genetic mapping of the sex-linked barring gene in the chicken Poult. Sci., September 1, 2009; 88(9): 1811 - 1817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kadariya, B. Yin, B. Tang, S. A. Shinton, E. P. Quinlivan, X. Hua, A. Klein-Szanto, T. I. Al-Saleem, C. H. Bassing, R. R. Hardy, et al. Mice Heterozygous for Germ-line Mutations in Methylthioadenosine Phosphorylase (MTAP) Die Prematurely of T-Cell Lymphoma Cancer Res., July 15, 2009; 69(14): 5961 - 5969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zheng, L. Gao, Y. Feng, L. Yuan, H. Zhao, and L. A. Cornelius Down-regulation of Rap1GAP via Promoter Hypermethylation Promotes Melanoma Cell Proliferation, Survival, and Migration Cancer Res., January 15, 2009; 69(2): 449 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Pasmant, I. Laurendeau, D. Heron, M. Vidaud, D. Vidaud, and I. Bieche Characterization of a Germ-Line Deletion, Including the Entire INK4/ARF Locus, in a Melanoma-Neural System Tumor Family: Identification of ANRIL, an Antisense Noncoding RNA Whose Expression Coclusters with ARF Cancer Res., April 15, 2007; 67(8): 3963 - 3969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hirasaki, T. Noguchi, K. Mimori, J. Onuki, K. Morita, H. Inoue, K. Sugihara, M. Mori, and T. Hirano BAC Clones Related to Prognosis in Patients with Esophageal Squamous Carcinoma: An Array Comparative Genomic Hybridization Study Oncologist, April 1, 2007; 12(4): 406 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hellerbrand, E. Bumes, F. Bataille, W. Dietmaier, R. Massoumi, and A. K. Bosserhoff Reduced expression of CYLD in human colon and hepatocellular carcinomas Carcinogenesis, January 1, 2007; 28(1): 21 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chattopadhyay, R. Zhao, E. Tsai, V. L. Schramm, and I. D. Goldman The effect of a novel transition state inhibitor of methylthioadenosine phosphorylase on pemetrexed activity. Mol. Cancer Ther., October 1, 2006; 5(10): 2549 - 2555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Bauer, P J Wild, S Meyer, F Bataille, A Pauer, M Klinkhammer-Schalke, F Hofstaedter, and A K Bosserhoff Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays J. Clin. Pathol., July 1, 2006; 59(7): 699 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Marce, O. Balague, L. Colomo, A. Martinez, S. Holler, N. Villamor, F. Bosch, G. Ott, A. Rosenwald, L. Leoni, et al. Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy. Clin. Cancer Res., June 15, 2006; 12(12): 3754 - 3761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Wild, S. Meyer, F. Bataille, M. Woenckhaus, M. Ameres, T. Vogt, M. Landthaler, A. Pauer, M. Klinkhammer-Schalke, F. Hofstaedter, et al. Tissue microarray analysis of methylthioadenosine phosphorylase protein expression in melanocytic skin tumors. Arch Dermatol, April 1, 2006; 142(4): 471 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Batova, H. Cottam, J. Yu, M. B. Diccianni, C. J. Carrera, and A. L. Yu EFA (9-beta-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine Blood, February 1, 2006; 107(3): 898 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hellerbrand, M. Muhlbauer, S. Wallner, M. Schuierer, I. Behrmann, F. Bataille, T. Weiss, J. Scholmerich, and A.-K. Bosserhoff Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma Carcinogenesis, January 1, 2006; 27(1): 64 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Laud, C Marian, M F Avril, M Barrois, A Chompret, A M Goldstein, M A Tucker, P A Clark, G Peters, V Chaudru, et al. Comprehensive analysis of CDKN2A (p16INK4A/p14ARF) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma J. Med. Genet., January 1, 2006; 43(1): 39 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Komyod, U.-M. Bauer, P. C. Heinrich, S. Haan, and I. Behrmann Are STATS Arginine-methylated? J. Biol. Chem., June 10, 2005; 280(23): 21700 - 21705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Subhi, B. Tang, B. R. Balsara, D. A. Altomare, J. R. Testa, H. S. Cooper, J. P. Hoffman, N. J. Meropol, and W. D. Kruger Loss of Methylthioadenosine Phosphorylase and Elevated Ornithine Decarboxylase Is Common in Pancreatic Cancer Clin. Cancer Res., November 1, 2004; 10(21): 7290 - 7296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Schuierer, F. Bataille, S. Hagan, W. Kolch, and A.-K. Bosserhoff Reduction in Raf Kinase Inhibitor Protein Expression Is Associated with Increased Ras-Extracellular Signal-Regulated Kinase Signaling in Melanoma Cell Lines Cancer Res., August 1, 2004; 64(15): 5186 - 5192. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
