Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature

Artikel i vetenskaplig tidskrift
Författare Nils J Fredriksson
Kerryn Elliott
Stefan Filges
Jimmy Van den Eynden
Anders Ståhlberg
Erik Larsson
Publicerad i Plos Genetics
Volym 13
Nummer/häfte 5
ISSN 1553-7404
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Sahlgrenska Cancer Center
Institutionen för kemi och molekylärbiologi
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Språk English
Länkar https://doi.org/10.1371/journal.pge...
Ämnesord human transcription factors, somatic mutations, cancer genomics, in-vivo, dna, binding, photoproducts, landscape, regions, search, Genetics & Heredity
Ämneskategorier Genetik

Sammanfattning

Sequencing of whole tumor genomes holds the promise of revealing functional somatic regulatory mutations, such as those described in the TERT promoter. Recurrent promoter mutations have been identified in many additional genes and appear to be particularly common in melanoma, but convincing functional data such as influence on gene expression has been more elusive. Here, we show that frequently recurring promoter mutations in melanoma occur almost exclusively at cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable exception. In active, but not inactive, promoters, mutation frequencies for cytosines at the 5' end of this ETS-like motif were considerably higher than expected based on a UV trinucleotide mutational signature. Additional analyses solidify this pattern as an extended context-specific mutational signature that mediates an exceptional position-specific vulnerability to UV mutagenesis, arguing against positive selection. We further use ultra-sensitive amplicon sequencing to demonstrate that cell cultures exposed to UV light quickly develop subclonal mutations specifically in affected positions. Our findings have implications for the interpretation of somatic mutations in regulatory regions, and underscore the importance of genomic context and extended sequence patterns to accurately describe mutational signatures in cancer.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?