A jumping gene with the fairy tale name "Sleeping Beauty" has helped
to unlock vital clues for researchers investigating the genetics of
colorectal cancer.
A study published today used the Sleeping Beauty transposon system
to profile the repertoire of genes that can drive colorectal cancer,
identifying many more than previously thought. Around one third of these
genes are mutated in human cancer, which provides strong evidence that
they are driver mutations in human tumours.
The collaborative project funded by Cancer Research UK and the
Wellcome Trust was led by Dr David Adams from the Wellcome Trust Sanger
Institute, and Dr Douglas Winton, of the Cancer Research-UK Cambridge
Research Institute.
"These findings, when combined with mutation data from human colon
cancers, will drive forward our understanding of the processes that lead
to colorectal cancer," says Dr Adams, senior author from the Sanger
Institute. "They demonstrate how many genes can contribute to this
cancer and how these genes work together in the development of this
disease".
The Sleeping Beauty transposon system induces genetic mutations at
random, identifying and tagging candidate cancer genes, the drivers that
cause colorectal cancer. This system has become critical in uncovering
the genetic pathways that cause cancer, and, in this study, the team
identify more than 200 genes that can be disrupted in human colorectal
cancers.
Colorectal (bowel) cancer is the third most common cancer in the UK,
and the second most common cause of cancer deaths after lung cancer;
just under 40,000 people were diagnosed with bowel cancer in the UK in
2008 – around 110 people every day – a figure which has shown little
improvement over the last decade.
"Our research provides a rich source of candidate genes that
represent potential diagnostic, prognostic and therapeutic targets, and
defines the breadth of genes that can contribute to cancer of the
intestine," says Dr Winton, senior author from the Cancer Research UK
Cambridge Research Institute. "It is becoming increasingly clear that
cancers are driven by mutations in disparate collections of genes and it
is essential that we tease apart the important changes."
Current thinking is that perhaps around 50 major drivers are mutated
in any one cancer cell, but the number and identity of all of the
cancer drivers, and how many drivers are found in each type of cancer,
is largely unknown. By performing screens for cancer genes in the mouse
and by then comparing them to data from human tumours the team
identified a rich catalogue of new candidate genes helping to refine the
genes that genetic pathways that drive bowel cancer development.
"At its heart, cancer is a disease driven by faulty genes," says Dr
Lesley Walker, director of cancer information at Cancer Research UK.
"Research suggests that each cancer cell has a number of 'driver' faults
that make them grow out of control, as well as 'passenger' faults that
they pick up as the disease develops. This technique is helping us to
tease out the key drivers of bowel cancer, laying the foundations for
more effective, targeted treatments for the disease in the future."
The research complements studies by The Cancer Genome Atlas and the
International Cancer Genome Consortium, which are cataloguing the
mutations responsible for cancer development using next generation DNA
sequencing.
