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Following initial characterization of the reference human genome, initiatives have evolved worldwide to identify genomic aberrations in cancer with the aim of deriving diagnostic, prognostic and predictive information. However, the functional and clinical relevance of many somatic variants in cancer are presently unknown and there is no consensus definition of 'actionability' for genomic aberrancies. Therefore, while robust detection of a variety of genetic aberrations in clinical specimens remains a technical hurdle, the greater challenge lies in the interpretation of these alterations. Critical evaluation of genomic variation in cancer requires the integration of available clinical and preclinical evidence related to their frequencies, functions and roles as therapeutic targets. Many publicly accessible data resources have compiled such evidence to facilitate the understanding of genomic results and ultimately translating results to clinical action. Information for these data resources is derived from various sources including large population genomic datasets, curation of published literature, and data sharing by the scientific community. Currently, there is no widely accepted guidance to definitively assess and integrate the diagnostic, prognostic and predictive information of somatic variants using these knowledge databases. This review will describe data resources pertinent to the identification and interpretation of actionable genomic aberrations by clinicians, and highlight relevant issues in the clinical application of tumor molecular profiling results. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Auditory development is disrupted without normal hearing but might proceed to some extent depending on the type and onset of deafness. We therefore hypothesized that activity in the auditory cortex would be highly variable in children who are deaf. Methods: To answer this, activity in the deaf brain was evoked by electrical pulses from newly provided bilateral cochlear implants (CIs) in 72 children (n =144 responses). Results: Responses were categorized by visual inspection into 3 main types which were validated by principal component cluster analyses; 49% had a negative amplitude wave similar to that previously reported in pre-term infants, 26% were dominated by a positive peak typical of responses in young normal hearing children and experienced paediatric CI users, 25% were novel multi-peaked responses. No significant demographic differences, including duration and onset of deafness, were found between response types. However, children with severe biallelic mutations of GJB-2 showed predominately negative peak type responses (79%) as compared with their peers without these mutations who had a more equal distribution between cortical response types. Conclusion: Cortical development in children who are deaf is heterogeneous but can be better predicted when the genotype is known to be a GJB-2 mutation. Significance: Remediation of childhood deafness seeks to restore normal development and function of central auditory functions and thus may need to be tailored to account for effects specific to the aetiology of deafness. [Copyright &y& Elsevier]