Lved in the pathogenesis of specific cancers) as opposed to that
Lved in the pathogenesis of specific cancers) as opposed to that of other AM genes, presumed not to be involved in the process (i.e., not candidates) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25636517 during apoptosis induction in K562 and SH-SY5Y.Page 29 of(page number not for citation purposes)BMC Medical Genomics 2009, 2:http://www.biomedcentral.com/1755-8794/2/nal transduction (e.g., HRAS, MAPK, PDCD6, YWHAE, YWHAG), metabolism, post-translational modifications (e.g., BECN1, MASK, RPL5, STK25) (Figure 1). Their biological role mainly consists in the regulation of the activity of receptors, transductors, and executors of the apoptotic program. Since they perform a critical role, these molecules were subjected to a strong selective pressure and have largely preserved structure and functions. In many cases, these proteins function within some of the most ancient biological processes: about 50 of these molecules are found in unicellular Eukaryotes and in Prokaryotes (e.g., the MAP kinases) [103]. Our data confirm results previously published on the evolution of the human genome: proteins operating in regulatory processes (e.g., transcription factors and receptors) have remained relatively well conserved during eukaryotic evolutions [104]. However, it remains true that the most conserved genes are those involved in such critical biological processes as metabolism, protein synthesis, and PD325901 biological activity molecular transport [104]. Our data seem also to suggest that in most of cancer models the genome regions most frequently affected by loss-type mutations contain the most conserved AM genes, suggesting a strong phenotype ?genotype correlation (see Results, Oncogenomics).Specificity of the AM transcriptome: cancer profiling The analysis of the AM transcriptome profile showed that the transcriptional involvement of this apparatus is heterogeneous in different cancer models for number and type of AM genes involved. These data suggest that AM could be involved in different tumours through tumour-specific mechanisms of transcriptional activation or repression [105,106]. According to our data, the main sources of AM transcriptional failure are represented by apoptosis regulators (i.e., transcription factors, kinases, and death receptors) rather than by its executors (e.g., members of the apoptosome, death transductors, and caspases) (Figure 7). This could suggest that frequently exploited mechanisms for cancer transformation are mutations of the genes at the top of the death signalling network: they are generally at the boundaries with other molecular machineries involved in cancer, such as the CCDRA or the DRM, and could have a pleiotropic effect on the activities of several other genes (Figure 7). The identification of specific AM molecular signatures (cancer profiling) could be useful for precise tumour diagnosis and specific therapy design, distinguishing the different molecular alterations associated to different tissues. As the number of AM genes transcriptionally altered in cancers is reasonably limited (between 25 and 200), specific low-cost platforms for AM transcriptome analysis could be designed for routine molecular screening of patients to understand the origin of the cancer and its metastases [107,108]. Furthermore, the comparison of molecular profiles would allow: (i) the identification of the common alterations among tumours;(ii) to understand the common basis of AM involvement in cancer transformation [107,108]. It is notable that a fraction of AM transcriptome dysregulations could be the resu.