Comprehensive characterization of RB1 mutant and MYCN amplified retinoblastoma cell lines

In retinoblastoma research tumor-derived cell lines remain an important model to investigate tumorigenesis and new therapy options, due to limited tumor material and lack of adequate animal models. A panel of 10 retinoblastoma cell lines was characterized with respect to mutation, methylation and expression of RB1 and MYCN. These established retinoblastoma cell lines represent the most frequent types of RB1 inactivation and together with the MYCN amplification status, three classes can be distinguished: RB1(mut)/MYCNnonA,RB1(mut)/MYCNA and RB1(wt)/MYCNA. MYCN amplification was identified in five cell lines, whereby two of them, RB522 and RB3823, harbor no aberration in RB1. Targeted sequencing of 160 genes often mutated in cancer identified only few variants in tumor-associated genes other than in RB1. None of these variants was recurrent. mRNA expression analyses of retinal markers, cell cycle regulators and members of the TP53 signaling pathway revealed a high variability between cell lines but no class-specific differences. The here presented thorough validation of retinoblastoma cell lines, including microsatellite analysis for cell line authentication, provides the basis for further in vitro studies on retinoblastoma

Innovation in Marketing Channels

In more recent years, the context of globalization in which market channel structures and strategies are developing is bringing to a more complex concept of marketing channels, with disintermediation or reintermediation, multichanneling and new roles/specializations that are emerging as new issues. In this context, innovation in marketing channels becomes a complex, multiorganizational, multidisciplinary activity that requires collaboration and interactions across various entities within the supply chain network. In recent years, the innovation processes in marketing channels have occurred with high intensity and speed, especially following the changes spurred by technology that allowed the adoption of more efficient organizational solutions