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Sci Rep. 2014 Apr 22;4:4743. doi: 10.1038/srep04743.

Mutated tumor alleles are expressed according to their DNA frequency.

Author information

1
TRON gGmbH - Translational Oncology at Johannes Gutenberg-University Medical Center gGmbH, Langenbeckstr. 1, Building 708, 55131 Mainz, Germany.
2
1] TRON gGmbH - Translational Oncology at Johannes Gutenberg-University Medical Center gGmbH, Langenbeckstr. 1, Building 708, 55131 Mainz, Germany [2] University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany.
3
1] TRON gGmbH - Translational Oncology at Johannes Gutenberg-University Medical Center gGmbH, Langenbeckstr. 1, Building 708, 55131 Mainz, Germany [2] BioNTech AG, Kupferbergterrasse 17-19, 55131 Mainz, Germany.
4
University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany.
5
1] TRON gGmbH - Translational Oncology at Johannes Gutenberg-University Medical Center gGmbH, Langenbeckstr. 1, Building 708, 55131 Mainz, Germany [2] University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany [3] BioNTech AG, Kupferbergterrasse 17-19, 55131 Mainz, Germany.

Abstract

The transcription of tumor mutations from DNA into RNA has implications for biology, epigenetics and clinical practice. It is not clear if mutations are in general transcribed and, if so, at what proportion to the wild-type allele. Here, we examined the correlation between DNA mutation allele frequency and RNA mutation allele frequency. We sequenced the exome and transcriptome of tumor cell lines with large copy number variations, identified heterozygous single nucleotide mutations and absolute DNA copy number, and determined the corresponding DNA and RNA mutation allele fraction. We found that 99% of the DNA mutations in expressed genes are expressed as RNA. Moreover, we found a high correlation between the DNA and RNA mutation allele frequency. Exceptions are mutations that cause premature termination codons and therefore activate nonsense-mediated decay. Beyond this, we did not find evidence of any wide-scale mechanism, such as allele-specific epigenetic silencing, preferentially promoting mutated or wild-type alleles. In conclusion, our data strongly suggest that genes are equally transcribed from all alleles, mutated and wild-type, and thus transcribed in proportion to their DNA allele frequency.

PMID:
24752137
PMCID:
PMC3994436
DOI:
10.1038/srep04743
[Indexed for MEDLINE]
Free PMC Article

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