Tumor Type

United Kingdom
Bone Cancer - Osteosarcoma / chondrosarcoma / rare subtypes
Funding Organizations
United Kingdom: The Wellcome Trust
United Kingdom: Skeletal Cancer Action Trust (Scat)
United Kingdom: Bone Cancer Research Trust
Netherlands: EuroBoNeT
Research Organizations
Research Activities
Publication Policy

1:   ICGC Goals, Structure, Policies and Guidelines Section E.3 - Publication Policy HTML 
2:   Template Letters to Facilitate Communications HTML 
to ensure appropriate dialogue between data users and generators and for authors to contact ICGC members and editors
Clinic & Pathology

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.

Sequencing & Analysis

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.

Complementary Studies

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.

Data Storage, Analysis & Management

United Kingdom: Wellcome Trust Sanger Institute

We will convert the summary datasets into ICGC compatible BioMart datasets.

Project Summary

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.

Principal Investigators

• Dr. P. J. Campbell
• Dr. P. A. Futreal
• Dr. A. M. Flanagan

Lead Jurisdiction