Tumor Type

United Kingdom
Breast Cancer - Triple Negative/lobular/other
http://www.sanger.ac.uk/  HTML
Project Profile
Funding Organizations
United Kingdom: The Wellcome Trust
United Kingdom: Breakthrough Breast Cancer
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
3:   WTSI Project Specific Moratorium HTML 
Clinic & Pathology

Australia: University of Queensland
Canada: BC Cancer Agency
France: Institut Curie
Institut National du Cancer (INCa)
Italy: National Cancer Institute Bari
Netherlands: AMC Medical Research BV
Erasmus University Rotterdam
Radboud University Nijmegen
Norway: Oslo University Hospital
University of Tromsø
Singapore: Singapore General Hospital
Sweden: Lund University
United Kingdom: Breakthrough Breast Cancer Research Unit, King’s College London
Cancer Research UK
Institute of Cancer Research
Wellcome Trust Sanger Institute
United States: Dana-Farber Cancer Institute
Sequencing & Analysis

United Kingdom: Wellcome Trust Sanger Institute
Complementary Studies

United Kingdom: Wellcome Trust Sanger Institute
Data Storage, Analysis & Management

United Kingdom: Wellcome Trust Sanger Institute
Project Publications
Project Summary

Breast cancer is the most common class of cancer diagnosed in women worldwide with more than one million cases diagnosed annually, is responsible for >400,000 deaths and is the leading cause of cancer deaths in women. The aetiology of most breast cancer cases is unknown. However, endocrine factors, inherited susceptibility and mutagenic exposures such as X-irradiation are all known to influence risk of the disease.

Histological, immunohistochemical, mRNA expression and genomic analyses have indicated that breast cancer is a heterogeneous disease composed of multiple biological subtypes. We have adopted a pragmatic working classification of breast cancer based on histology combined with immunohistochemistry for a limited biomarker set including estrogen receptor (ER), progesterone receptor (PR) and HER2. This classification is outlined below.

The Wellcome Trust and Breakthrough Breast Cancer have funded this proposal which focuses on triple negative breast cancers.

Classification scheme of breast cancer
• ER-, HER2-, PR- (triple negative)
• ER-, HER2+ tumors
• ER+, HER2+ tumors
• ER+, HER2-, PR+ tumors; ductal-type
• ER+, HER2-, PR- tumors; ductal-type
• Invasive lobular carcinoma
• “Rare” histological special types

We propose to generate comprehensive catalogues of somatic mutations in 500 triple negative breast cancers under the ICGC model by high coverage, shotgun genome sequencing of both tumor and normal DNA. All classes of mutations are expected to be detected including base substitutions, insertions, deletions, copy number changes, translocations and other chromosomal rearrangements. These catalogues of mutations will afford us statistical power to identify cancer genes that are mutated at a frequency of greater than 3% in this class of breast cancer. They will also carry signatures of past mutagenic processes operative in the development of each cancer and thus provide insights into the aetiology of the disease.

Complementary catalogues of epigenomic changes (genome-wide DNA methylation) will be generated for the same 500 cancer samples together with mRNA and miRNA expression profiles. Integrated analyses of these data will be carried out and compared to parallel datasets from other classes of breast cancer as well as other types of cancer.

The ICGC Breast Cancer Working Group will be overseeing this study and others focusing on breast cancer subtypes and is funded through a number of sources including the European Commission FP7 (ER+ve breast cancer) and the Institut Nationale du Cancer (HER2+ve cases) in addition to this Wellcome Trust and Breakthrough Breast Cancer funded proposal on triple negative breast cancer.

Principal Investigators

Michael Stratton

Lead Jurisdiction