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A P16(ink4a)-insensitive Cdk4 Mutant Targeted By Cytolytic T-lymphocytes in a Human-melanoma

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Wolfel, T. Hauer, M. Schneider, Jenny [UCL] Serrano, M. Wolfel, C. De Plaen, Etienne [UCL] Beach, D.

A mutated cyclin-dependent kinase 4 (CDK4) was identified as a tumor-specific antigen recognized by HL4-A2.1-restricted autologous cytolytic T lymphocytes (CTLs) in a human melanoma. The mutated CDK4 allele was present in autologous cultured melanoma cells and metastasis tissue, but not in the patient's lymphocytes. The mutation, an arginine-to-cysteine exchange at residue 24, was part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 inhibitor p16(INK4a), but not of p21 or of p27(KIP1). The same mutation was found in one additional melanoma among 28 melanomas analyzed. These results suggest that mutation of CDK4 can create a tumor-specific antigen and can disrupt the cell-cycle regulation exerted by the tumor suppressor p16(INK4a).

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1995
Language Anglais
Journal information "Science" - Vol. 269, no. 5228, p. 1281-1284 (1995)
Peer reviewed yes
Publisher Amer Assoc Advan Science (Washington)
issn 0036-8075
e-issn 1095-9203
Publication status Publié
Affiliation UCL - FSA/MECA - Département de mécanique
Links
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Bibliographic reference Wolfel, T. ; Hauer, M. ; Schneider, Jenny ; Serrano, M. ; Wolfel, C. ; et. al. A P16(ink4a)-insensitive Cdk4 Mutant Targeted By Cytolytic T-lymphocytes in a Human-melanoma. In: Science, Vol. 269, no. 5228, p. 1281-1284 (1995)
Permanent URL http://hdl.handle.net/2078.1/47865