CancerGenome
NEWS FEATURE
NATURE|Vol
Vol 464|15 April 2010
The
ANCER
GEN ME
challenge
Interchromosomal rearrangement Point mutation
Y
1
X
22
2
9
10
7
8
Intrachromosomal rearrangement Copy-number change
© 2010 Macmillan Publishers Limited. All rights reserved
needle pulled from a veritable haystack of cancer-associated mutations thanks to highpowered genome sequencing. In the past two years, labs around the world have teamed up to sequence the DNA from thousands of tumours along with healthy cells from the same individuals. Roughly 75 cancer genomes have been sequenced to some extent and published; researchers expect to have several hundred completed sequences by the end of the year.
The efforts are certainly creating bigger haystacks. Comparing the gene sequence of any tumour to that of a normal cell reveals dozens of single-letter changes, or point mutations, along with repeated, deleted, swapped or
3 inverted sequences (see ‘Genomes at a glance’). “The difficulty,” says Bert
Vogelstein, a cancer researcher at the
Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins,
4
“is going to be figuring out how to use the information to help people rather than to just catalogue lots and lots of mutations”. No matter how
5
similar they might look clinically, most tumours seem to differ genetically. This stymies efforts to distinguish
6
the mutations that cause and accelerate cancers — the drivers — from the accidental by-products of a cancer’s growth and thwarted
DNA-repair mechanisms — the passengers.
Researchers can look for mutations that pop up again and again, or they can identify key pathways that are mutated at different points. But the projects are providing more questions than answers. “Once you take the few obvious mutations at the top of the list, how do you make
adapted from m. r. Stratton, p. J. Campbell & p. a. futreal Nature 458, 719–724 (2009).
Circos plots can give a snapshot of the mutations within a genome. The outer ring represents
NATURE|Vol
Vol 464|15 April 2010
The
ANCER
GEN ME
challenge
Interchromosomal rearrangement Point mutation
Y
1
X
22
2
9
10
7
8
Intrachromosomal rearrangement Copy-number change
© 2010 Macmillan Publishers Limited. All rights reserved
needle pulled from a veritable haystack of cancer-associated mutations thanks to highpowered genome sequencing. In the past two years, labs around the world have teamed up to sequence the DNA from thousands of tumours along with healthy cells from the same individuals. Roughly 75 cancer genomes have been sequenced to some extent and published; researchers expect to have several hundred completed sequences by the end of the year.
The efforts are certainly creating bigger haystacks. Comparing the gene sequence of any tumour to that of a normal cell reveals dozens of single-letter changes, or point mutations, along with repeated, deleted, swapped or
3 inverted sequences (see ‘Genomes at a glance’). “The difficulty,” says Bert
Vogelstein, a cancer researcher at the
Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins,
4
“is going to be figuring out how to use the information to help people rather than to just catalogue lots and lots of mutations”. No matter how
5
similar they might look clinically, most tumours seem to differ genetically. This stymies efforts to distinguish
6
the mutations that cause and accelerate cancers — the drivers — from the accidental by-products of a cancer’s growth and thwarted
DNA-repair mechanisms — the passengers.
Researchers can look for mutations that pop up again and again, or they can identify key pathways that are mutated at different points. But the projects are providing more questions than answers. “Once you take the few obvious mutations at the top of the list, how do you make
adapted from m. r. Stratton, p. J. Campbell & p. a. futreal Nature 458, 719–724 (2009).
Circos plots can give a snapshot of the mutations within a genome. The outer ring represents