The information below refers to the time of the award.
Born 1957 in the United Kingdom, Michael Stratton studied medicine at the University of Oxford and Guy’s Hospital, London. Following internships, he trained as a histopathologist and subsequently obtained his PhD in molecular biology of cancer at the Institute of Cancer Research, London. There, in 1991, he set up an independent faculty group focusing on cancer susceptibility. Six years later, he was made professor of Cancer Genetics and chair of the newly constituted Section of cancer Genetics. In 2000, he moved to the Wellcome Trust Sanger Institute as Head of the Cancer Genome Project and was named Director of the Institute in 2010.
Michael Stratton was elected Fellow of the UK Academy of Medical Sciences in 1999 and of the Royal Society in 2008. He is also a member of EMBO (the European Molecular Biology Organization). His research on cancer has won him numerous distinctions in Europe and in the USA. He was notably awarded the Lila Gruber Award for Cancer Research by the American Academy of Dermatology, the C. Chester Stock Award by Memorial Sloan Kettering Cancer Center and the Massachusetts General Hospital Award in Cancer Research.
All cancers have their origins in defective genes. When genes are modified (or suffer mutations), they disrupt the way cells work, either causing them to divide in an uncontrolled manner, or to continue to live when they should normally autodestruct (apoptosis). They then end up spreading around and invading the organism. In other words mutated genes – cancer genes – change a normal cell into a cancer cell.
As certain cancer genes can be hereditary, Michael Stratton studied families where breast cancer had occurred frequently. In this way he identified one of the main causes: the gene BRCA2. This gene is now routinely checked in order to identify those persons at risk, to guard against the disease and, should it occur, to treat it more effectively.
Michael Stratton then looked at genetic modifications that build up throughout a person’s lifetime, known as somatic mutations. Taking advantage of the decoding on the human genome, he involved his team in a major experiment across the whole human genome, seeking to identify the mutated genes leading to all types of cancers. He has thus identified a large number of these mutated genes, and notably the BRAF gene present in six out of ten skin cancers.
These somatic mutations that build up throughout everyone’s lifetime constitute a kind of “archaeological chronicle”, as they contain the record of each cancer cell’s life history. Michael Stratton has decided to track down the origin of these mutations. Are the causes environmental or linked with lifestyle, or are they due to the body’s internal biochemical processes? Unravelling this mystery is important; it will allow us to understand the fundamental causes of cancer.
One in three people in the developed world will suffer from cancer and one in four die of the disease. Whether an individual develops cancer depends on many factors. Some cancers are linked with environment and lifestyle – such as tobacco consumption or exposure to carcinogenic substances; others are caused by hereditary factors resulting in a predisposition to develop the disease and then there are still others that are due to chance. Whatever the initial cause, however, all cancers are induced by changes to the genetic inheritance present in each cell of the body. They originate from changes –mutations – in our DNA.
Numerous genes (approximately 2% of all those that make up our genetic inheritance) have an important role in controlling how cells behave. When they undergo mutations, they function abnormally and lead cells to divide when they should not do so, to remain alive when they should die (apoptosis), and finally to proliferate and spread around the body. In other words, these mutated genes convert a normal cell into a cancer cell. This is why they are called “cancer genes”.
A mutation in a cancer gene is sometimes inherited from a parent. If so, it is present in every cell of the body and causes the person and their family to have an increased risk of developing cancer.
In his early work, Michael Stratton focused his efforts on understanding hereditary predispositions to developing cancer. In particular, he studied families with breast cancer cases, tracking down and identifying one of the major mutated genes responsible, calledBRCA2. This gene and its mutations are now routinely checked by clinical geneticists, to identify women with high risk of developing breast cancer in order to prevent or treat the disease.
As we go through life, mutations occur in the DNA of each individual cell of our body. If any of these affect a cancer gene, it will convert a healthy cell into a cancer cell.
Over some three decades, numerous researchers have sought to identify these cancer genes. Michael Stratton introduced a new approach to achieving this. Based on the decoded DNA sequence of the human genome, which had been finalised in the year 2000, the British researcher proposed using the DNA sequence thus discovered as a template against which to compare the DNA sequences of cancer cells. To achieve this he set up a major experiment – the Cancer Genome Project – searching for mutations across the whole human genome and across all cancer types.
Using this approach Michael Stratton and his colleagues found many new mutated cancer genes. One of the genes thus discovered has had particular impact for patients: theBRAF gene exhibits mutations in 60% of cases of malignant melanoma, a serious type of skin cancer The component of the cellular machinery made by BRAF controls whether cells divide or not. Under normal circumstances it is switched “ON” or “OFF” according to signals from outside the cell. Mutations in BRAF, however, block it in the “ON” position, continuously telling cells to divide and thus to proliferate.
Michael Stratton speculated that BRAF would be a promising target for development of a drug against malignant melanoma, a disease resistant to conventional forms of treatment. Eight years later, the first effective drug based on this approach has now been developed, showing remarkable benefits in patients suffering from melanoma.
Michael Stratton continues to use genome sequences to understand how cancers arise. Somatic mutations in the DNA of each individual cell of the body build up throughout everyone’s lifetime. They therefore represent a chronicle of each cancer’s life history, tracing the different stages of its development. As a ‘chronicler’ of this evolution, this British researcher is seeking out what caused the mutations in the first place. Was it environmental or life style phenomena, or the body’s internal biochemical processes? Much of this still remains a mystery, but finding the answers is important and could lead Michael Stratton to discover the fundamental causes of the disease.
Fig. 1. Accumulation of mutations in a lifetime from fertilized egg to malignant cancer cell
This graphic represents changes, during a lifetime, that accumulate in a descendant of a fertilized egg that eventually becomes a fully malignant cancer cell. Mutations in cancer cells are of two main types. Some can drive the development of the cancer – ‘driver’ mutations, with perhaps one to ten required for fully malignant cancer (represented as gear wheels’ above). Others are ‘passenger’ mutations that are part of the damage to the cell genome but do not contribute to cancer development and number tens of thousands in many cancer cells examined to date (represented as ‘lozenges’ above). Each colour is used to represent mutations at a different time in different genes. Driver mutations can be valuable targets for new drug development and their identification can serve to improve diagnosis. The many passenger mutations tell the story of the mutational events the cell has passed through and help to classify tumours and identify cancer-causing events or exposures.
Published in EMBO Molecular Medicine (2013) 5: 1–4 and used with permission.
PET scans of a patient treated for metastatic malignant melanoma with a drug that targets mutated BRAF. The positron-emission tomography scan at the left was taken before treatment: cancers are visualized as dark areas. The bladder and kidney outflows are also dark because of accumulation of dye. The scan at the right was taken after 15 days’ treatment with Vemurafenib, a selective inhibitor of mutated BRAF and shows dramatic reduction in the number and activity of detected cancers.
© Grant McArthur, Peter MacCallum Cancer Centre. Used with permission.
Professeur Michael Stratton
Wellcome Trust Sanger Institute
Wellcome Trust Genome Campus
Cambridge CB10 1SA (UK)
Tél. +44 1223 494 757 (direct)
Tél +44 1223 494 739 (assistante)