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

Motion style acupuncture therapy for shoulder pain: a randomized controlled trial

Guang-Xia Shi,1 Bao-Zhen Liu,2 Jun Wang,3 Qing-Nan Fu,1 San-Feng Sun,2 Rui-Li Liang,2 Jing Li,3 Jian-Feng Tu,1 Cheng Tan,3 Cun-Zhi Liu4 1Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing100010, China; 2Acupuncture and Moxibustion Department, Beijing Huairou District Hospital of Traditional Chinese Medicine, Beijing 101400, China; 3Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing100010, China; 4Department of Acupuncture and Moxibustion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China Background: Strategies for preventing the persistence of pain and disability beyond the acute phase in shoulder pain patients are critically needed. Conventional acupuncture therapy (CAT) or motion style acupuncture therapy (MSAT) alone results in relative improvements in painful conditions in shoulder pain patients; combined interventions may have more global effects. The aim of this study is to evaluate the efficacy and safety of MSAT vs CAT for shoulder pain. Methods: A randomized controlled trial using a factorial design was conducted from January 2014 to December 2015. Patients with a primary complaint of one-sided shoulder pain participated at three study sites. Eligible individuals were randomly assigned to receive MSAT plus minimal CAT (mCAT), CAT plus minimal MSAT (mMSAT), MSAT plus CAT, or mMSAT plus mCAT for 6 weeks in a 1:1:1:1 ratio. The primary outcome was change in shoulder pain intensity (measured using visual analog scale). The secondary outcomes included change in function of the shoulder joint (Constant–Murley score) and the health-related quality of life (Short Form-36 Health Survey). Moreover, perceived credibility of acupuncture was measured using the Treatment Credibility Scale. The outcomes were assessed at baseline and at 6, 10, and 18 weeks after randomization. Analysis of covariance with the baseline score adjustment had been used to determine the primary end point. The between-group differences of MSAT vs mMSAT and CAT vs mCAT were estimated, respectively, after tests of interaction between the two-dimensional interventions. All main analyses followed the intention-to-treat principle. Results: A total of 164 patients completed the study. MSAT was superior to mMSAT in alleviating pain intensity at 10 weeks (P=0.024), and it was maintained for 18 weeks (P=0.013). Statistically significant differences were found when comparing MSAT with mMSAT for improvement in shoulder function (6 weeks, P=0.01; 10 weeks, P=0.006; and 18 weeks, P=0.01), physical health (10 weeks, P=0.023 and 18 weeks, P=0.015), and mental health (18 weeks, P=0.05). No significant differences were found in CAT when compared with mCAT. Conclusion: After 18 weeks of treatment, pain and joint functions are improved more with MSAT than with minimal motion style acupuncture or conventional acupuncture in patients with shoulder pain. Keywords: motion style acupuncture, shoulder pain, acupuncture therapy, randomized controlled tria