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Content archived on 2024-06-18

Why do cancers occur where they do? A genetic and evolutionary approach.

Objective

Tumorigenesis is a form of somatic evolution, a topical subject given the advent of cancer genome sequencing. However, we contend that some features of Darwinian evolution have been neglected when cancer is studied, as have some aspects of evolution that are special to cancers. For example, tumours comprise an expanding population of cells, cancers must occur within a normal human lifespan, and genotypes detrimental to growth of the tumour as a whole may be selected. These factors may render invalid the classical model in which successive mutations with large advantages arise and spread through the tumour in selective sweeps. To incorporate these neglected features and to test how tumorigenesis depends on factors such as mutation rate, selection and size constraints, we shall set up a comprehensive model of tumour growth incorporating cell birth, death, division and mutation parameters. We shall examine specific aspects of cancer-as-evolution in mice. By marking mutant clones using fluorescent proteins, we can track them and see how they persist, spread and die. We shall also determine the mutation profiles and genetic diversity of mutant clones and whole tumours in mice and humans using next-generation sequencing. Specific experiments will determine: (i) the fate of new advantageous clones arising in an existing tumour; (ii) whether new disadvantageous clones can persist in tumours; (iii) whether apparently maladaptive traits for tumour growth, such as suppressing the growth of competitors, can be selected; (iv) why do housekeeper gene mutations cause cancer in specific sites; (v) can cancer cells have too much genomic instability; and (vi) whether all cancers develop owing to driver mutations with big effects, or are there “mini-drivers” of tumorigenesis? There will be continual cross-talk between the experimental and modelling work. The results of the project will enhance our basic understanding of tumorigenesis and suggest strategies for anticancer therapy.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2013-ADG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-AG - ERC Advanced Grant

Host institution

THE UNIVERSITY OF BIRMINGHAM
EU contribution
€ 1 511 570,08
Address
Edgbaston
B15 2TT Birmingham
United Kingdom

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Region
West Midlands (England) West Midlands Birmingham
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (2)

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