Bladder Cancer - Invasive Urothelial Bladder Cancer 
Breast Cancer - Subtype defined by an amplification of the HER2 gene 
Breast Cancer - Ductal carcinoma 
Breast cancer - Asian phenotype 
Pediatric Brain Tumors - Medulloblasma & Pediatric Pilocytic Astrocytoma 
Brain Cancer - Pediatric Medulloblastoma 
Colorectal cancer - Adenocarcinoma, non-Western 
Oral Cancer - Gingivobuccal 
Thyroid Cancer - Papillary thyroid carcinoma 
Chronic Lymphocytic Leukemia - CLL with mutated and unmutated IgVH 
Liver Cancer - Hepatocellular carcinoma (Virus associated) 
Ovarian Cancer - Serous cystadenocarcinoma 
Rare Pancreatic Tumors - Enteropancreatic endocrine tumors and rare pancreatic exocrine tumors 
| United Kingdom: | Royal National Orthopaedic Hospital NHS Trust |
| Netherlands: | Leiden University Medical Center |
| Norway: | Oslo University Hospital |
| United Kingdom: | Nuffield Orthopaedic Centre NHS Trust |
| UCL Cancer Institute | |
| University College London Hospitals |
This group will collect and assess samples and clinical data from patients for inclusion in the study.
| United Kingdom: | Wellcome Trust Sanger Institute |
Second/third generation sequencing technologies will be employed to generate the detailed sequence of the cancer so that it can be analysed bioinformatically in order to identify the differences between the cancer and a normal cell.
| United Kingdom: | Wellcome Trust Sanger Institute |
Complementary studies will include screeing for DNA copy number aberrations using state of the art high-density SNP-based microarray technology, generation of genome-wide profiles for DNA methylation through methyl cap fractionation. Finally Gene expression profiling using shotgun tag sequencing (RNA-Seq) along with Chromatin- and DNA methylation-enriched tag sequencing (ChIP-seq, MethylCap-seq and MeDIP-seq) will also be carried out.
| United Kingdom: | Wellcome Trust Sanger Institute |
We will convert the summary datasets into ICGC compatible BioMart datasets.
Osteosarcoma accounts for approximately 35% of primary malignant bone tumours. It occurs in adolescents and young adults but also extends into middle and old age. There is substantial histological heterogeneity with multiple subclasses recognised. Osteosarcoma is treated with surgery and neoadjuvant chemotherapy and the five year survival is ~50%. Mutations of RB (10%), CDKN2A (10%) and TP53 (30%) have been reported in osteosarcoma, but no other known cancer genes are commonly mutated.
Chondrosarcoma accounts for approximately 25% of primary malignant bone tumours. Conventional central and peripheral chondrosarcomas represent close to 90% of all chondrosarcomas, and are a relatively homogeneous histological subtype but appear to be genetically distinct with loss of function of EXT1 and EXT2 being implicated in the pathogenesis of the latter. Rare histologically distinct subclasses including mesenchymal, clear cell, periosteal and dedifferentiated variants also exist. Tumour grade is the single most important predictor of local recurrence and metastasis that has been identified to date. Chondrosarcoma Grade 1 rarely metastasises and this disease is associated with close to 100% survival, whereas the 5 year survival for patients with Grade 3 chondrosarcoma is approximately 10%. To date recurrent mutations have not been identified other than in CDKN2A.
We propose to generate comprehensive catalogues of somatic mutations in 250 osteosarcomas, 200 chondrosarcomas and 50 rarer bone tumour types.
The ICGC Bone Tumour Cancer Working Group will oversee this study.
Dr. P. A. Futreal
Dr. A. M. Flanagan