John C. Castle, Martin Loewer, Sebastian Boegel, Arbel D. Tadmor, Valesca Boisguerin, Jos de Graaf, Claudia Paret, Mustafa Diken, Sebastian Kreiter, Özlem Türeci & Ugur Sahin. Mutated tumor alleles are expressed according to their DNA frequency. Nature Scientific Reports. 4:4743. DOI: 10.1038/srep04743
Mainz, May 14, 2014 – Therapy selection for cancer patients often depends on the presence or absence of a specific DNA mutation. However, if the mutation is not transcribed RNA, as could be the case for heterozygous mutations, the utility of a DNA-based assay may be compromised. In a just-published report in Nature’s Scientific Reports, TRON researchers have shown that DNA mutations are indeed transcribed to RNA. Using next-generation sequencing to examine genome-wide mutations and transcription, they show that the DNA mutations are transcribed in proportion to their underlying DNA mutation allele fraction. For example, if a mutation is present on 3 of 4 alleles in a tetraploid genomic segment, 75% of the transcripts will contain the mutation. The primary implication is that monitoring mutations with DNA is acceptable for patient therapy selection.