(Written by Iñigo Martincorena, Cancer Genome Project, Wellcome Trust Sanger Institute Cambridge, UK)
In the year 2001, the sequence of the human
genome was announced as a milestone in science history. This represented a
nearly complete map of the common genetic information in all of us. The project
had taken over 10 years, the work of thousands of scientists around the globe,
and it had cost approximately 3,000 million euros. This huge effort marked the
beginning of a genomic revolution in biology.
Although it provided an unprecedented
wealth of information, a single reference sequence for all humans contained
little information on what makes each of us different or on the basis of
genetic diseases. Since then, however, sequencing technologies have evolved
dramatically. Nowadays, a person can be sequenced in a few days for less than
1,000 euros, and the cost continues to drop rapidly. This has allowed us to go
from a single reference human genome to sequencing many thousands of people, unravelling
the basis of many diseases and bringing us much closer to an era of
personalised genomics in the clinic.
A field that has benefited enormously from
the boom of sequencing technologies is cancer research. Cancer is largely
caused by mutations that accumulate in our cells throughout life, which make
every tumour unique. Genome sequencing can be used to catalogue the entire list
of mutations in a cancer, providing a detailed understanding of the basis of
any given tumour. The first genome of a cancer was sequenced in 2009 at the
Sanger Institute (Cambridge, United Kingdom), where I work as a postdoctoral
researcher. Just 6 years later, over 10,000 cancers have been sequenced
throughout the world, providing a detailed catalogue of the genes altered across
a wide range of cancer types. And this number is predicted to increase to
several hundred thousand in the next few years. This is proving to be an
invaluable resource for cancer research and, as we continue to learn how to use
this vast information, it will significantly improve cancer diagnosis and
therapy.
We have now learned that the genome of a
cancer typically contains between 1,000 to 20,000 acquired mutations. Of these,
only a handful of mutations (called driver mutations) are believed to be directly
responsible for the cancer, having affected key genes that control the normal
proliferation of cells. Remarkably, while we have a detailed understanding of
the mutations present in many cancers, we still know very little about how
normal cells begin to accumulate these mutations as they evolve into cancer.
At the Sanger Institute, we are beginning
to explore the mutations present in normal tissues to better understand how
cancer emerges from healthy cells. In a study that we published last month, we
used new sequencing techniques to reveal for the first time the mutations
present in normal skin from healthy individuals. Surprisingly, we found far
more mutations that we expected to see in a normal tissue. We found that normal
cells from sun-exposed skin contain many thousands mutations, even more than
many tumours. The majority of these mutations were caused by ultraviolet rays
from exposure to the sun. More surprisingly, we found that over a quarter of
the cells in sun-exposed skin had already acquired one cancer-driver mutation
and so had given a first step towards becoming a cancer. These cells formed
small clones that grew slightly faster than other cells in the skin, and we
found over 100 such clones in every square centimetre of sun-exposed skin. Despite
this number of cancer mutations in normal skin was a big surprise, almost certainly none of these cells
would have developed into skin cancer during the lifetime of these individuals.
Our bodies have very strict controls against cancer and these mutant cells were
still a few steps away from being able to form a tumour. Yet, you can help your
body and protect yourself against skin cancer by remembering to put on sunscreen
when you step out in the sun this summer.
This study of normal skin gave us an
unprecedented look into the first steps that skin cells take to become cancerous.
In addition to continuing sequencing cancer genomes, at the Sanger Institute we
now plan to extend this work on normal cells into other organs. Understanding
the frequency of cancer mutations in normal cells from different parts of the
body and in different people would help us better understand how cancer emerges,
and perhaps identify ways to detect cancer early or prevent it.
The potential of genome sequencing is
enormous but it is still mainly restricted to research institutions. However,
with the rapidly lowering cost of the technology and the constant development
of new applications, we should expect genome sequencing to be adopted by
hospitals within the next few years. The revolution of genomics offers exciting
opportunities for patients, hospitals and industry, but also poses a
significant challenge to universities and students. Making sense of genomic
data requires a good background in biology, computer programming and
statistics, still an uncommon mix in most biology or medical degrees. Yet, such
mixed training should be actively promoted in universities to take full
advantage of the many opportunities that lie ahead in the genomic revolution.
Iñigo Martincorena
BIO & BCH '07
No comments:
Post a Comment