Regular Article

British Journal of Cancer (2000) 82, 818–822. doi:10.1054/bjoc.1999.1005 www.bjcancer.com
Published online 20 January 2000

Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A, P14ARF or cdk4 genes

N Soufir1,*, B Bressac-de Paillerets1, L Desjardins2, C Lévy2, J Bombled1, I Gorin3, P Schlienger4 and D Stoppa-Lyonnet5

  1. 1Unité des Marqueurs Génétiques des Cancers, Institut Gustave Roussy, 45 rue Camilles Desmoulins, Villejuif, F94805 cedex, France
  2. 2Service d'Oncologie Ophtalmologique, 26 rue d'Ulm, Paris, F75231, France
  3. 3Consultation de Dermatologie, 26 rue d'Ulm, Paris, F75231, France
  4. 4Service de Radiothérapie C, 26 rue d'Ulm, Paris, F75231, France
  5. 5Service de Génétique Oncologique, Institut Curie, 26 rue d'Ulm, Paris, F75231, France

*Present address: Institut de Recherche Sur la Peau, Inserm U312, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, Paris, F75010, France

Received 2 June 1999; Revised 27 September 1999; Accepted 28 September 1999.

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Abstract

In familial cutaneous malignant melanoma (CMM), disruption of the retinoblastoma (pRB) pathway frequently occurs through inactivating mutations in the p16 (p16INK4A/CDKN2A/MTS1) gene or activating mutations in the G1-specific cyclin dependent kinase 4 gene (CDK4). Uveal malignant melanoma (UMM) also occurs in a familial setting, or sometimes in association with familial or sporadic CMM. Molecular studies of sporadic UMM have revealed somatic deletions covering the INK4A-ARF locus (encoding P16INK4Aand P14ARF) in a large proportion of tumours. We hypothesized that germline mutations in the p16INK4A, p14ARFor CDK4 genes might contribute to some cases of familial UMM, or to some cases of UMM associated with another melanoma. Out of 155 patients treated at the Institut Curie for UMM between 1994 and 1997, and interviewed about their personal and familial history of melanoma, we identified seven patients with a relative affected with UMM (n = 6) or CMM (n = 1), and two patients who have had, in addition to UMM, a personal history of second melanoma, UMM (n = 1), or CMM (n = 1). We screened by polymerase chain reaction single-strand conformation polymorphism the entire coding sequence of the INK4A-ARF locus (exon 1alpha from p16INK4A, exon 1beta from p14ARF, and exons 2 and 3, common to both genes), as well as the exons 2, 5 and 8 of the CDK4 gene, coding for the functional domains involved in p16 and/or cyclin D1 binding. A previously reported polymorphism in exon 3 of the INK4A-ARF locus was found in one patient affected with bilateral UMM, but no germline mutations were detected, either in the p16INK4A, p14ARFor CDK4 genes. Our data support the involvement of other genes in predisposition to uveal melanoma. © 2000 Cancer Research Campaign

Keywords:

uveal melanoma, germline mutation, P16INK4A, P14ARF, cdk4

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