Abstract
A novel candidate tumor suppressor gene, TTC4, on chromosome 1p31 has been described recently. Since aberrations in this region have been detected in malignant melanoma, we investigated DNA of paraffin-embedded sections from 16 typical naevi, 19 atypical naevi, 32 primary melanomas (15 superficial spreading melanomas, 17 nodular melanomas) and 25 metastases and DNA from four melanoma cell lines by PCR and direct sequencing analysis for mutations in all exons of TTC4. Tumors comprised a wide range of thickness (Breslow index) and Clark levels. No mutations could be detected in typical or atypical naevi, but we found seven different point mutations in the tumor samples, six of them causing an amino acid change. Ten melanoma samples belonging to nine patients showed one or more of these mutations. In detail, in six of 25 metastases, in two of 17 nodular melanomas and in two of 15 superficial spreading melanomas point mutations could be detected. In two cell lines, a loss of a whole exon could be demonstrated and in one cell line we found a point mutation. In addition, three polymorphisms were found. Our findings indicate that TTC4 may participate in the pathogenesis of malignant melanomas of the skin.
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References
Albino AP, Lloyd KO, Houghton AN, Oettgen HF and Old LJ. . 1981 J. Exp. Med. 154: 1764–1778.
Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Lin L-Y and Patterson C. . 1999 Mol. Cell. Biol. 19: 4535–4545.
Blatch GL and Lässle M. . 1999 Bioessays 21: 932–939.
Chen MX, McPartlin AE, Brown L, Chen YH, Barker HM and Cohen PT. . 1994 EMBO J. 13: 4278–4290.
Dracopoli NC, Harnett P, Bale SJ, Stanger BZ, Tucker MA, Housman DE and Keffort RF. . 1989 Proc. Natl. Acad. Sci. USA 86: 4614–4618.
Fransen M, Brees C, Baumgart E, Vanhooren JC, Baes M, Mannaerts GP and Van Veldhoven PP. . 1995 J. Biol. Chem. 270: 7731–7736.
Heim S and Mitelman F. (ed). . (1995). Cancer Cytogenetics: Chromosomal and molecular genetic aberrations of tumor cells. 2nd Ed. Wiley-Liss: New York.
Honore B, Leffers H, Madsen P, Rasmussen HH, Vandekerckhove J and Celis JE. . 1992 J. Biol. Chem. 267: 8485–8491.
Isfort RJ, Cody DB, Doersen CJ, Richards WG, Yoder BK, Wilkinson JE, Kier LD, Jirtle RL, Isenberg JS, Klounig JE and Woychik RP. . 1997 Oncogene 15: 1797–1803.
Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F and Sumimoto H. . 1999 J. Biol. Chem. 274: 25051–25060.
Lam E, Martin M and Wiederrecht G. . 1995 Gene 160: 297–302.
Poetsch M, Woenckhaus C, Dittberner T, Pambor M, Lorenz G and Herrmann FH. . 1998 Lab. Invest. 78: 883–888.
Poetsch M, Woenckhaus C, Dittberner T, Pambor M, Lorenz G and Herrmann FH. . 1999 Virch. Archiv. 435: 105–111.
Poetsch M, Dittberner T and Woenckhaus C. . 2000 Cancer Genet. Cytogenet. (in press).
Schrick JJ, Onuchic LF, Reeders ST, Korenberg J, Chen XN, Moyer JH, Wilkinson JE and Woychik RP. . 1995 Hum. Mol. Genet. 4: 559–567.
Siracky J, Blasko M, Borovansky J, Kovarik J, Svec J and Vrba M. . 1982 Neoplasma 29: 661–668.
Su G, Roberts T and Cowell JK. . 1999 Genomics 55: 157–163.
Su G, Casey G and Cowell JK. . 2000 Int. J. Mol. Med. 5: 197–200.
Thompson FH, Emerson J, Olson S, Weinstein R, Leavitt SA, Leong SPL, Emerson S, Trent JM, Nelson MA, Salmon SE and Taetle R. . 1995 Cancer Genet. Cytogenet. 83: 93–104.
Wiltshire RN, Duray P, Bittner ML, Visakorpi T, Meltzer PS, Tuthill RJ, Liotta LA and Trent JM. . 1995 Cancer Res. 55: 3954–3957.
Zhang H and Grishin NV. . 1999 Protein Sci. 8: 1658–1667.
Acknowledgements
We thank Dr S Burchill for providing the cell lines DX3, MEWO, and LT5.1, and Prof Dr K Schallreuther and Dr N Hibberts for providing the cell line M19. We thank S Seefeldt, M Maschke, and M Richter for excellent technical assistance.
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Poetsch, M., Dittberner, T., Cowell, J. et al. TTC4, a novel candidate tumor suppressor gene at 1p31 is often mutated in malignant melanoma of the skin. Oncogene 19, 5817–5820 (2000). https://doi.org/10.1038/sj.onc.1203961
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DOI: https://doi.org/10.1038/sj.onc.1203961
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