Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(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 promoter(4); 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 evolution(7); 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).Peer reviewe

A Disease Without History? Evidence for the Antiquity of Head and Neck Cancers

There has been a long-running debate in anthropological, archaeological, and medical literature regarding the prevalence of cancer in various ancient human populations. At one extreme, some scholars have claimed that past human societies had rates of cancer roughly equivalent to those seen among modern peoples; at the other extreme, some researchers have effectively claimed that cancer is a disease of modernity. The present study aims to shed further light on this topic, at least insofar as cancers of the head and neck are concerned. A review of ancient art, medical texts, and paleopathological reports revealed somewhat discordant accounts of the age, geographical distribution, and prevalence of head and neck cancers. While representations of these neoplastic conditions in art are relatively rare and patchy in geographic distribution, descriptions of suspect lesions in ancient medical texts are rather more widespread, if unevenly distributed geographically, and the paleopathological record was found to contain surprisingly abundant evidence for cancers of the head and neck, especially as compared to what are, in modern societies, more ubiquitous cancers of the breast, lung, or prostate. While establishing the absolute prevalence of any of these conditions in antiquity is impossible, the present work establishes that cancers of the head and neck have long been present, and perhaps even prevalent, in human societies