Integrative and comparative genomics identifies novel melanoma tumor-suppressor genes

A cardinal feature of melanoma is its metastatic propensity. Paucity of insights into the genetic events that drive metastasis has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. Recent approaches that integrate human genomic and transcriptomic data provide unprecedented opportunities to discover oncogenic drivers in melanoma. However, the radically altered and complex cytogenetic profile of human melanoma makes the identification of such drivers particularly challenging. There is therefore a pressing need for developing biologically meaningful approaches that would facilitate the identification and validation of the driver lesions. We propose to combine comparative oncogenomics with an innovative mouse model to identify new bona fide cancer genes/pathways that drive melanoma progression and metastasis. Spontaneously acquired genetic alterations such as copy-number alterations and specific point mutations in mouse tumours of defined genetic origin will be used to prioritize relevant lesions from the complex human melanoma genomes. Priority will be given to lesions involving modifiers of the p53 tumour suppressor and non-coding RNAs as we are particularly interested in the contribution of these molecules to cancer development. Critically, a somatic cell gene delivery mouse model will be developed for rapid validation of the genetic alterations in an appropriate in vivo context.status: publishe

Evaluation of optical features of the macula in multiple sclerosis

Purpose Differences in optical and irregularity measures of abnormal retinal tissue may provide additional information of impairment of the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer complex (GCL+IPL) in multiple sclerosis (MS). The purpose of our study was to estimate these retinal changes in MS. Methods Twenty‐seven patients with MS were examined using Stratus OCT. The raw macular OCT data was exported and processed using OCTRIMA software and the fractal dimension (FD) and layer index (LI) values of seven intraretinal layers were obtained. The enrolled eyes were divided into two groups, based on ON in the history (ON+ group, n=13 and ON‐ group, n=14). Data of 73 healthy subjects (N) were used as controls. ANOVA with Newman‐Keuls post‐hoc analysis was used for the comparison of FD and LI values. The level of significance was set at p<0.001. Results A significant decrease was observed in LI in the entire macula and the perifoveal region in RNFL (12.4±1.4, 10.8±0.8, 9.3 ±1.4 and 14.0±1.7, 12.0±0.9, 10.0±1.7 for the N, ON‐ and ON+ groups, respectively). The RNFL in the ON‐ group was significantly different from both the N and ON+ groups (p<0.001 for all comparisons). No significant changes were found in the other layers. A significant increase was observed between the ON‐ and ON+ groups in FD in the entire macula and the perifoveal region in the RNFL layer (1.8±0.04, 1.8±0.07 p<0.001 and 1.6±0.06, 1.6±0.1 p<0.001, respectively) but no significant changes were found in the other layers. Conclusion In MS, the optical features of the ganglion cells and the RNFL also change besides the pathological remodeling of macular tissue. This result may help to improve the diagnostic efficacy of OCT in MS. Commercial interes

Non-coding RNA networks in cancer

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions