Frequent mutation of the FOXA1 untranslated region in prostate cancer View Full Text


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Article Info

DATE

2018-12

AUTHORS

Matti Annala, Sinja Taavitsainen, Gillian Vandekerkhove, Jack V W Bacon, Kevin Beja, Kim N Chi, Matti Nykter, Alexander W Wyatt

ABSTRACT

Prostate cancer has a low somatic mutation rate but non-coding regions remain underexplored. We sequenced the untranslated regions (UTRs) of 72 established driver genes in 428 patients with metastatic prostate cancer and identified FOXA1 3'-UTR mutations in 12% of patients. The mutations were predominantly insertions or deletions, covered the entire UTR without motif enrichment, and were not detected in other cancers. FOXA1 lies in head-on orientation with the androgen-regulated non-coding gene AL121790.1, resulting in strong prostate lineage-specific bidirectional transcription across the FOXA1 3'-UTR. This suggests transcriptional activity as a cause for the localized hypermutation. The indel-dominant pattern of somatic mutation extends into the FOXA1 coding region, where it is shaped by clonal selection to yield a cluster of non-frameshift indels inside the forkhead domain. Somatic FOXA1 3'-UTR mutations may prove useful for diagnostic and screening approaches, given their high frequency and lineage specificity. More... »

PAGES

122

References to SciGraph publications

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  • 2012-04. Fast gapped-read alignment with Bowtie 2 in NATURE METHODS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s42003-018-0128-1

    DOI

    http://dx.doi.org/10.1038/s42003-018-0128-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106257238

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30272002


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