• Colorectal cancer
• colorectal metastases
• genotype

Colorectal cancer arises from normal epithelial cells lining the large intestine. Turning normal epithelial cells into cancer cells requires extensive reprogramming of their biological properties in order to make them survive as tumour cells, an evolutionary process driven by changes at the (epi)genetic level. Concepts from tumour biology teach that the processes involved include increased proliferation, evasion of apoptosis, disruption of cell cycle check points, disruption of basal membrane, cell motility, remodelling of the extra-cellular matrix and recruiting new stroma, including angiogenesis, and on top of this, escape from the immune system. Basically, tumour cells need to be proficient in these processes for producing both a primary invasive cancer and metastatic outgrowths.

Two hypotheses exist as to how tumour cells acquire the (epi)genomic programmes that determine their ultimate fate; that is, whether or not metastasis will occur. According to one model, tumour cells sequentially first acquire the (epi)genetic alterations that render them premalignant lesions; next, alterations occur that are necessary to become invasive; and thereafter, when a primary cancer has already become fully established, cells would acquire by further stochastic mutations the properties necessary to produce metastasis. An alternative …