Thursday 06 Mar 2014Ecological modelling of cancer evolution

Dr Yinyin Yuan - Institute of Cancer Research, London

Harrison 103 15:00-16:00

Heterogeneity in the cancer ecosystem is thought to promote cancer evolution and enhance progression. To systematically investigate this in patient tumours, We have developed a quantitative measurement of intra-tumour heterogeneity in the cancer microenvironment based on automated image-based morphological analysis. We showed that this measurement based on Hematoxylin & Eosin stained primary tumour sections predicts 10-year disease-specific survival in two independent sample sets of high-grade breast cancers. Our analysis revealed a novel independent poor prognosis subgroup characterised by a highly heterogeneous cancer ecosystem. Integration of this measurement with genome-wide copy-number data identified copy-number loss of 4q14 to be significantly enriched in this subgroup. Patients with heterogeneous microenvironment and loss of 4p14 had 5-year disease-specific survival rate of less than 20%. Increased filopodia and loss of cell adhesion were observed upon siRNA silencing of 4p14 genes in non-malignant MCF10A cells, suggesting a possible mechanism for the poor prognosis. Our data support the contention that ecological forces contribute to cancer evolution and prognosis.

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