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  • cancerfoe cancerfoe Feb 21, 2013 9:41 PM Flag

    Telomerase and Melanoma (not "pumping", just an interesting study

    TERT Promoter Mutations in Familial and Sporadic Melanoma
    Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Iris Moll, Nagore E, Hemminki K, Schadendorf D, Kumar R.

    Science 22 February 2013:
    Vol. 339 no. 6122 pp. 959-961
    DOI: 10.1126/science.1230062
    Published Online January 24 2013

    Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription. We then screened the TERT promoter in sporadic melanoma and observed recurrent ultraviolet signature somatic mutations in 125 of 168 (74%) of human cell lines derived from metastatic melanomas, 45 of 53 corresponding metastatic tumor tissues (85%), and 25 of 77 (33%) primary melanomas. The majority of those mutations occurred at two positions in the TERT promoter and also generated binding motifs for Ets/TCF transcription factors.

    Sentiment: Hold

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