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Cancer, DNA

Step-by-step: determining the development of cancer

There are over 200 different types of cancer, with 1 in the 3 people in the UK being affected by the disease during their lifetime. Cancer is caused by an accumulation of multiple alterations to the genetic material inside a cell, and these changes can vary widely even between individuals suffering from the same form of cancer. This complexity makes cancer a hugely challenging disease to treat, and therefore there is an evident need for scientists to continue their research to improve our understanding of this disease. Raffaella Facchini describes the development of a novel tool by researchers in Terry Rabbitts’ lab at the WIMM that could help scientists study how and why cancers develop.

Cancer is a disease that arises when changes, known as mutations, occur in the genetic material (DNA) that is found inside all cells of the body. DNA contains all the information required for the body to function normally, therefore these changes can have a dramatic impact on our health. One of the ways mutations can arise is via a process known as chromosomal translocation.

Steps

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DNA does not exist as a single entity in each cell; it is packaged into discrete structures called chromosomes that are arranged in pairs. Twenty-two of these pairs look the same between men and women whilst the 23rd pair differ, as this pair determines the gender of the individual. Each of the chromosome pairs contains DNA that encodes different information in the form of smaller, individual regions called genes.

During the development of cancer, parts of chromosomes from different pairs can be shuffled around and rearranged. The underlying genetic information is therefore altered, leading to the fusion of distinct genes which would usually function independently. This process is known as chromosomal translocation, and the gene fusions that result from it can then give rise to abnormal cellular functions that often lead to the development of tumours.

To study changes like these which often occur in cancers such as sarcomas (cancers of the bone or muscle) or leukaemias and lymphomas (cancer of the blood), the Rabbitts’ group have developed a system to generate specific chromosomal translocations in an extremely fast, high-throughput way, in cells which are then easily accessible to researchers to use for further study. Importantly, they have been able to make several step-by-step changes to the DNA in the same order they occur in patients. By making these changes to the DNA sequentially, they were able to mimic the development of the cancer exactly as it occurs in humans.

As these cells contain the same mutations as found in patients, they can be used as models for certain human cancers and therefore provide a novel system for safely and efficiently testing new drugs and therapeutic strategies for some of the world’s most deadly diseases.

Post edited by Bryony Graham.

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