https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:55819 Wed 26 Jun 2024 16:17:41 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:55817 Wed 26 Jun 2024 16:10:47 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:29578 Wed 17 Nov 2021 16:29:30 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:46707 1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter⁴; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation^5,6; analyses timings and patterns of tumour evolution⁷; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity^8,9; and evaluates a range of more-specialized features of cancer genomes^8,10-18.]]> Tue 29 Nov 2022 11:22:06 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:54322 Tue 20 Feb 2024 15:58:30 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:42354 Mon 22 Aug 2022 14:01:38 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:55957 0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. Results: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P =.02), worse biochemical recurrence (subdistribution HR, 2.39; P =.003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P =.005), and worse overall survival (HR, 4.51; P =.05). Conclusions: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.]]> Fri 12 Jul 2024 10:25:39 AEST ]]>