Splicing aberration of TP53 transcripts in cancers: mechanisms and effects
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AbstractTP53 is a very important tumour suppressor gene. Germline mutations caused familial cancer syndromes. There are also somatic mutations causing non-sense, frame-shift and premature termination found in various cancers. However, little is known about splicing aberration in cancer.
Methods: The RNA-seq data in the TCGA dataset was screen for transcripts with novel splicing sites in the TP53 gene. Their prevalence, location, origin of the tumor and effects on disease prognosis were analyzed.
Results: There are 28 known transcript variants for TP53. In addition, we identified 7 novel transcripts. 71% of them led to a frame-shift in the protein coding sequence. The transcript causing a splicing aberration between exon 7 and exon 8 was recurrent in 30 tumour samples. These tumours were originated from breast, lung, colon and thyroid tissues. We then investigated the mechanism responsible for this splicing event. All of the samples with high expression level of this novel transcript could be explained by one of the 2 somatic mutations near the splicing sites. Namely, a C to A mutation at the splicing acceptor site and a C to A/G mutation at the 6bp downstream of the end of intron 7.
Finally, we compared the survival of patients with or without this splicing aberration. It was found that breast cancer patients without splicing aberration have a better survival.
Conclusion: Analysis of RNA-seq of cancer transcriptome provides important information about the gene expression and variation of transcripts. It also provides a means to assess the functional consequence of somatic mutations and characterize novel transcripts.
All Author(s) ListDan Huang, Fu Yan Hu, Nelson Tang
Name of ConferenceThe 21st Annual International Conference on Research in Computational Molecular Biology (RECOMB) 2017
Start Date of Conference03/05/2017
End Date of Conference07/05/2017
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
LanguagesEnglish-United Kingdom

Last updated on 2018-04-07 at 11:46