Comprehensive genomic characterization defines human glioblastoma genes and core pathways.

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer

Humphrey Center News: Spring 1989 v. 4, no. 1

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Humphrey Center News: Spring 1991 v. 6, no. 1

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Humphrey Center News: Winter 1990 v. 5, no. 2

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Humphrey Center News: Fall 1989 v. 4, no. 2

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Humphrey Center News: Spring 1988 v. 3, no. 1

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Humphrey Center News: Spring 1990 v. 5, no. 1

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

A retrospective cohort study of the influence of lifestyle factors on survival of patients undergoing surgery for colorectal cancer.

Aim: Several modifiable and non-modifiable health related behaviours are associated with the incidence of Colorectal Cancer (CRC), but there is little research on their association with survival. The project aimed to investigate possible relationships between modifiable behavioural factors and outcomes on a study cohort of CRC patients undergoing potentially curative surgery. Method: A retrospective cohort study was carried out of patients diagnosed with non-metastatic CRC undergoing elective curative surgery (January 2011 - December 2012), residing in the NHS Greater Glasgow & Clyde (NHSGGC) area, UK. Data were obtained from the Scottish Cancer Registry, National Scottish Death Records. Pre-operative assessment of smoking, alcohol consumption, nurse-measured body mass index (BMI) and exercise levels were recorded and patients were followed until death or censorship. Survival analysis was carried out and proportional hazards assumptions were assessed graphically using plots and were then formally tested using the PHTEST procedure in STATA. Results: Of the initial 527 patients, 181 (34%) satisfied the inclusion criteria. The total duration of follow up was 480 person-years. At the pre-operative assessment, 75% were overweight or obese, 10.6% were current smokers, 13.1% recorded excess alcohol consumption and 8.5% had physical difficulty climbing stairs. Age, BMI, histopathological stage and physical capacity all independently affected survival (P<0.05). Overweight patients (HR 2.81) and those who had difficulty climbing stairs (HR 3.31) had a significantly poorer survival. Conclusion: The study found evidence that pre-operative exercise capacity and BMI are important independent prognostic factors of survival in patients undergoing curative surgery for CRC

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Humphrey Center News: Spring 1985 v. 1, no. 1

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine