Abstract
Recently, the retinoblastoma protein interacting zinc finger gene RIZ has been proposed as a candidate for the tumor suppressor locus on 1p36, because of the common loss of RIZ1 RNA in human tumors. In addition, frameshift mutations of this gene have been demonstrated in a variety of tumors with microsatellite instability. Since alterations in this region have been described in malignant melanomas, we investigated DNA of paraffin-embedded sections from 16 typical naevi, 19 atypical naevi, 33 primary melanoma lesions and 25 metastases and DNA from four melanoma cell lines by PCR and direct sequencing analysis of RIZ. Frameshift mutations in the RIZ gene were found in 17% of melanoma samples and 8.6% of naevi, but we could not demonstrate any missense mutations in the exons of RIZ1. No LOH of the RIZ gene nor any microsatellite instability in six dinucleotide markers or in the mononucleotide repeats IGRIIR, hMSH3, and hMSH6 could be demonstrated in the samples with RIZ frameshift mutations. Although our results do not explain the high rate of deletions in 1p36 found in this tumor, they assign RIZ a potential role in the multi-step tumor forming process of malignant melanoma of the skin.
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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 and M Maschke for excellent technical assistance. The authors would also like to thank two anonymous reviewers for their useful comments.
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Poetsch, M., Dittberner, T. & Woenckhaus, C. Frameshift mutations of RIZ, but no point mutations in RIZ1 exons in malignant melanomas with deletions in 1p36. Oncogene 21, 3038–3042 (2002). https://doi.org/10.1038/sj.onc.1205457
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DOI: https://doi.org/10.1038/sj.onc.1205457
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