Significance of duon mutations in cancer genomes

Abstract

Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed “duon mutations” due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.

Thermodynamic evidence for a field-angle-dependent Majorana gap in a Kitaev spin liquid

“…However, the peak in the temperature dependence of specific heat at ∼ 100 K well above T N is characterized by an entropy release of (R/2) ln 2 (R is the gas constant) [12,13], and Raman scattering spectra show fermionic responses [14,15], which have been explained by fractionalized excitations consistent with the Kitaev model. Several experimental studies have found that the application of magnetic field in the honeycome plane can suppress the ZZ order with a critical field of ∼ 7 T [16,17], above which a paramagnetic state appears. Most notably, in a limited field (H) and temperature (T ) range of this field-induced paramagnetic state, the field-dependent thermal Hall conductivity measurements [18][19][20] have revealed a plateau behavior with the value close to one half of quantized thermal Hall conductivity of electronic system.…”

Structural and functional analysis of somatic coding and UTR indels in breast and lung cancer genomes

“…found that at least 14% of coding regions in human genomes can bind transcription factors 50 . The prevalence of such sequences and their implication in diseases suggest their important roles in human genomes and diseases 47 – 49 , 51 . Third, we compared the conservation score distributions of CDS and UTR indels between cancer genomes and healthy genomes.…”

“…About 15% of codons in the human genome were hypersensitive to DNase I treatment, suggesting the existence of likely dual-use sequences for both amino acid coding and transcriptional regulation 50 . These dual function sequences, termed as duons, were considered to be more conserved than non-duon coding sequences and mutations in these duons could lead to diseases 50 , 51 .…”

Genomic Abelian Finite Groups

“…Four possible group representations for this exon subregion are suggested in the top of the figure (panel a). These types of protein-coding regions are called duons, since their base-triplets encode information not only for aminoacids but also for transcription enhancers [32][33][34]. Fig.…”