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Cancer gene mutation more complex than previously thought
Source: Agencies |
March 16, 2012, Friday
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TAKING a sample or biopsy from just one part of a tumor might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.
A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumor, and yet further gene differences in samples taken from secondary tumors.
That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumor disease like breast, lung, or kidney cancer that has spread to others parts of the body.
But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.
The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumor.
They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumor and also from other organs where the tumor had spread.
They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumor.
Samples taken from secondary tumors - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumor sample is not sufficient.
"We've known for some time that tumors are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study.
He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumors and within a single patient, with more differences between biopsies from the same tumor than similarities.
"The next step will be to understand what's driving this diversity in different cancers and identify key driver mutations that are common throughout all parts of a tumor," Swanton said.
A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumor, and yet further gene differences in samples taken from secondary tumors.
That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumor disease like breast, lung, or kidney cancer that has spread to others parts of the body.
But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.
The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumor.
They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumor and also from other organs where the tumor had spread.
They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumor.
Samples taken from secondary tumors - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumor sample is not sufficient.
"We've known for some time that tumors are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study.
He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumors and within a single patient, with more differences between biopsies from the same tumor than similarities.
"The next step will be to understand what's driving this diversity in different cancers and identify key driver mutations that are common throughout all parts of a tumor," Swanton said.
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