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

Tratamento ortodôntico-cirúrgico da assimetria facial esquelética: relato de caso Orthodontic-surgical treatment of skeletal facial asymmetry: case report

INTRODUÇÃO: as assimetrias faciais representam um desequilíbrio entre as estruturas esqueléticas homólogas da face. A maioria das pessoas apresenta algum grau de assimetria facial, pois é rara a condição de perfeita simetria. Todavia, somente quando é perceptível aos olhos do paciente, essa assimetria passa a ser relevante. Em tal condição, a correção ortocirúrgica ou o tratamento ortodôntico são possibilidades normalmente adotadas. OBJETIVO: o presente trabalho, baseado em uma revisão de literatura, é ilustrado por um caso clínico cujo tratamento consistiu em cirurgia ortognática Le Fort I para avanço e rotação da maxila e, na mandíbula, o tratamento foi conservador. CONCLUSÃO: o conhecimento da queixa principal e da expectativa do paciente e exames de diagnóstico bem realizados são itens importantes na decisão do plano de tratamento e no sucesso do resultado final.<br>INTRODUCTION: Facial asymmetries consist of an imbalance between the homologous skeletal structures of the face. Most people present some degree of facial asymmetry, since a state of perfect symmetry is rare. This common asymmetry only becomes relevant when it is perceivable by the patient. In this situation, either orthodontic surgical correction or orthodontic treatment is normally chosen. OBJECTIVE: This study, based on literature review, has been illustrated by a case report comprising Le Fort I orthognathic surgery for maxillary advancement and rotation, with conservative treatment for the mandible. CONCLUSION: Knowledge of the patient's chief complaint and expectations, as well as proper diagnostic exams, are important factors to decide the treatment plan and for the final treatment outcome