Understanding Diverse Evolutionary Trajectories Within Breast Tissues
Research type
Research Study
Full title
High-Resolution Multi-omic Studies to Understand Breast Cancer Development and Progression in the Context of Normal Tissue Processes
IRAS ID
276860
Contact name
David Adams
Contact email
Sponsor organisation
Wellcome Sanger Institute
Duration of Study in the UK
5 years, 6 months, 28 days
Research summary
Throughout a lifetime each cell in the human body is continuously exposed to damaging insults that can alter its DNA, or genetic-code. When this damage escapes repair, or repair is inaccurate this can result in permanent changes in the DNA that are known as somatic mutations. Somatic mutations can activate or inactivate certain genes, known as cancer genes.
Within any given cancer, all cells are genetically related and consequently share hundreds to thousands of somatic mutations. Genetic diversity within the cancer arises through the ongoing accumulation of private mutations in individual cells and the subsequent division of the cell. Consequently breast cancers constitute patchworks of genetically related yet distinct groups of cells, termed subclones. A number of genomic sequencing studies have demonstrated that the aggressive features of a breast cancer, including invasiveness, treatment resistance and metastasis frequently arise from detectable subclones in the original primary breast tumour. However these are not always localised to the most aggressive subclones.
We wish to study subclone growth patterns to see how they vary over space, time, and in relation to their environment. This includes looking at how factors such as gestation, lactation and menopause affect breast development. We will use spatially resolved molecular analyses and draw on a range of technologies including genomic, transcriptomic and other approaches to study both normal tissues (women) and breast cancers (men and women) from the earliest stage of disease (pre-invasive), through to the stages of tissue invasion and distant metastasis.
The nature, and scarcity, of the human tissue samples needed to address the complex questions requires international and national collaborations. We have established collaborations with researchers in the UK and Norway who have collections of samples donated with relevant meta data in the context of clinical trials with consent and/or ethical approval for use in future research.
REC name
London - Harrow Research Ethics Committee
REC reference
20/PR/0905
Date of REC Opinion
26 Jan 2021
REC opinion
Favourable Opinion