The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

Summary Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting deployment of molecularly targeted treatments with reduced toxicities. Prior studies failed to disclose the full spectrum of driver genes and molecular processes operative in MB subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific driver alterations including previously unappreciated actionable targets. Driver mutations explained the majority of Group 3 and Group 4 patients, remarkably enhancing previous knowledge. Novel molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions targeting KBTBD4 and ‘enhancer hijacking’ driving PRDM6 activation. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB patients.

Real Time PCR. Univariate analysis showed that higher expression levels of hsa-miR-30a-3p, hsa-miR30c and hsa-miR-182 were significantly associated with benefit of tamoxifen treatment and with longer PFS (all P-values < 0.01). In multivariate analysis, corrected for the traditional predictive factors, only hsa-miRNA-30c was an independent predictor (P-value < 0.01). Finally, in an attempt to understand the biology connected to this miRNA, Global testing pathway analysis showed an association of hsa-miRNA30c expression with HER and RAC1 signaling pathways.We identified hsa-miRNA-30c as an independent predictor for clinical benefit of tamoxifen therapy in patients with advanced breast cancer. Assessment of tumor levels and connected pathways could be helpful to improve treatment strategies.3