UCL Cancer Institute Seminar Series

Genetic diversification and clonal selection are thought to underlie tumour initiation, progression and resistance, but their dynamics are poorly characterized. Although direct observations of human tumour growth are impractical, tumours encode their
ancestries in the form of somatic alterations acquired during cell division, which can be exploited through multi-region sampling to infer their evolutionary trajectories.

Recently, we described a novel ‘Big Bang’ model of primary human colorectal tumour growth, whereby after transformation, the neoplasm grows predominantly as a single expansionproducing numerous intermixed sub-clones and where the timing of a mutation is the fundamental determinant of its frequency in the final tumour. Through spatial computational modelling and statistical inference, we demonstrate that the majority of detectable intra-tumour heterogeneity occurs during the earliest stages of tumour growth. This new model is compatible with effectively neutral evolution and explains the dynamics of colorectal tumour growth with significant clinical implications.

I will describe extensions of this work to delineate mechanisms of disease progression and the importance of accounting for tumour growth dynamics when interpreting cancer genomic data.

Curtis lab

Hosted by Dr Javier Herrero

The seminar will be followed by a sandwich buffet lunch 

References

1. Kang H, Salomon MP, Sottoriva A, Zhao J, Toy M, Press MF, Curtis C, Marjoram P, Siegmund K, Shibata D. Many private mutations originate from the first few divisions of a human colorectal adenoma. J Pathology, 2015. 

2. Sottoriva A, Kang H, Ma Z, Graham TA, Salomon M, Zhao J, Marjoram P, Siegmund K, Press MF, Shibata D & Curtis C. A Big Bang Model of human colorectal tumor growth. Nature Genetics, 2015.

3. Curtis C. Genomic Profiling of breast cancers. Curr Opin Obstet Gynecol, 27(1), 2015.
 

Location

UCL Cancer Institute
Courtyard Café
Paul O'Gorman Building 
72 Huntley Street
London, WC1E 6DD