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

Thymic Surgery in Jamaica: 1992-2000: Cirugía Tímica en Jamaica 1992-2000

The treatment for thymic tumours and/or myaesthenia gravis (MG) includes thymectomy. Controversy exists as to the optimal timing and operative approach to thymectomy. At the University Hospital of the West Indies, Kingston, Jamaica, the results of thymic surgery during the period 1992 to 2000 were studied retrospectively. There were 26 patients operated on, 17 females and nine males. Twenty-three underwent thymectomy to treat MG, and three to remove a thymoma. The average age for females was 30.7 years, and 25.1 years for males. Average duration of symptoms prior to surgery was 16 months (all patients), and the interval between diagnosis and referral averaged 2.6 months. All patients underwent thymectomy via median sternotomy with a cervical extension of the incision if required. A policy of phrenic nerve preservation, even if residual tumour was left behind, was followed. Patients with thymomas were given post-operative radiotherapy. Chemotherapy was not given to any patient. The medium and long term results of thymic surgery in a developing country are presented. The results are within international norms, although the small patient population makes statistical analysis difficult. There appears to be no need to change current practice, despite the reported efficacy of less invasive approaches to thymic surgery. El tratamiento para tumores del timo y/o la miastenia gravis (MG) incluye la timectomía. Existe controversia en relación con el tiempo óptimo y el enfoque operativo de la timectomía. En el Hospital Universitario de West Indies, Kingston, Jamaica, se estudiaron los resultados de cirugía del timo durante el periodo de 1992 al 2000 retrospectivamente. Un total de 26 pacientes – 17 mujeres y 9 hombres – operados. Veintitrés fueron sometidos a timectomía para tratar la MG, y tres para extirpar un timoma. La edad promedio de las mujeres fue de 30.7 años, y la de los hombres 25.1 años. La duración promedio de los síntomas antes de la cirugía fue de 16 meses (todos los pacientes), y el intervalo entre el diagnóstico y la remisión al especialista promedió 2.6 meses. Todos los pacientes sufrieron timectomia via estemotomía media con extensión cervical de la incisión en caso de ser necesario. Se siguió como política la preservación del nervio frénico, aun cuando quedara tumor residual. A los pacientes con timomas se les aplicó radioterapia postoperatoria. No se administró quimioterapia a ningún paciente. Se presentan los resultados de la cirugía tímica a medio y largo plazo en un país en vías de desarrollo. Los resultados están dentro de las normas intemacionales, aunque la pequeña muestra poblacional de pacientes hace difícil el análisis estadístico. No parece haber necesidad de cambial la práctica actual, a pesar de los reportes en cuanto a la eficacia de tratamientos menos invasivos en la cirugía tímica