Heterogeneity in tumours

Cancer has long been understood to be a clonal disease, where almost all spontaneous tumours originate from a single mutated cell. It is striking therefore to observe the extent of genetic and phenotypic heterogeneity exhibited by the majority of human tumours upon diagnosis. A single tumour most commonly consists of multiple (sub)populations of cells, each with a unique genetic profile (intra-tumour heterogeneity). On the next level, tumours of the same anatomical origin and with the same clinical diagnosis from different patients are also known to show large variation in genetic profiles (inter-tumour heterogeneity).

Both these kinds of heterogeneity have biological and clinical implications for the treatment and management of cancer. Clonal diversity may provide a broader genetic base on which selection can occur, potentially seeding tumour evolution and therapeutic escape. Clinically, the co-existence of distinct clones in a tumour with potentially different responses to a particular treatment is important knowledge in management of the disease.

Here at the Department of Molecular Oncology, we have several projects underway which aim to address these issues, in colorectal, prostate and ovarian cancer. In all these cancer types, the tumours are sampled at multiple loci, and the individual biopsies characterized genetically. With this as our starting material, we compare the profiles generated from different loci within a single tumour, and from tumours from different patients and hope to gain insight into the role of heterogeneity in these diseases.