DNA-based assays are often more robust than RNA-based assays, and whereas the mutation spectrum causing TSG inactivation is usually diverse (which limits the utility of mutation-specific detection strategies for tumor screening programs), TSG inactivation by promoter hypermethylation provides a more homogeneous target for molecular screening strategies.
These include neuronal differentiation and, as a consequence, RETT syndrome, a disorder of the autism spectrum caused by mutation of methyl CpG binding protein MeCP2, which has been modeled using genetic engineered cells.
It is intriguing that the disease spectrum caused by VCP mutations similarly includes both ALS and FTD and that TDP-43 pathology occurs prominently in VCP linked disease.
Analysis of the mutation spectrum of TP53, caused by various environmental factors, and the resulting tumor spectrum are valuable for elucidating cancer etiology (Olivier et al., 2010).
Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation.
This deep sequencing analysis of mutation spectrum demonstrated that BaP causes primarily guanine transversions (e.g. G C → T A), which is highly consistent with previous studies employing Sanger sequencing.
We previously demonstrated that the NPCB used in this study generate free radicals, induce DNA strand breaks, and increase mutation frequency in FE1mouse lung epithelial cells in vitro, and that the mutation spectrum is in keeping with mutations caused by ROS [Jacobsen et al., 2007, 2008, 2010].
It follows that, should some of the remaining MCRA cases be caused by a defect in DNA repair or by some other form of hypermutation, the somatic mutation spectrum will reflect the underlying cause of genomic instability.
Explanations in terms of positive selection, or more subtle artifacts caused by changes in the mutation spectrum, cannot be entirely excluded.
