体液测定可检测某些癌症
Mutated mitochondrial DNA can be found in bodily fluids and may lead to simpler diagnosis of some cancers, according to a report in the March 17th issue of Science.
High levels of mitochondrial DNA (mtDNA) are ubiquitous in human cells, the authors explain, and most copies of mtDNA are identical at birth. Furthermore, the entire gene sequence must be expressed to maintain proper mitochondrial function, "suggesting that even slight alterations in DNA sequences could have profound effects."
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Dr. David Sidransky and colleagues from Johns Hopkins University School of Medicine in Baltimore, Maryland, analyzed 14 human bladder tumors, 13 head and neck tumors, and 14 lung primary tumors for mtDNA mutations and compared the results with mtDNA from samples of bodily fluids.
The scientists report their detection of 292 mtDNA sequence variations, 196 of which represented previously recorded polymorphisms and 57 of which were previously unknown polymorphisms. "The remaining 39 variants were acquired (somatic) mutations identified in 64%...of the bladder cancer patients, 46%...of the head and neck cancer patients, and 43%...of the lung cancer patients," the investigators note.
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Mutant mtDNA derived from tumor tissues was found in all three urine samples obtained from patients with bladder cancer, in two thirds of the saliva samples from patients with head and neck cancer, and in 8 of 10 bronchoalveolar lavage samples from patients with lung cancer.
"In addition," the researchers report, "several of the bladder and head and neck cancers studied here had multiple mutations, implying possible accumulation of mtDNA damage."
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A considerable number of the mtDNA mutations were localized in the displacement-loop (D-loop) region, a key site for both replication and expression of the mt genome, the results indicated.
"Although additional investigation is needed to define the functional importance of mt mutations, our data establish that these mutations are frequent and present at high levels in all of the tumor types examined," the authors conclude. "Because of its high copy number, mtDNA may provide a distinct advantage over other nuclear genome-based methods for cancer detection."
, 百拇医药
"With a mt genome that‘s only around 16 kb, it should be fairly straightforward to determine which mutations associate with which kinds of tumors," Dr. Sidransky told Reuters Health. "The whole process is also helped by the fact that virtually every cell that falls off into the body fluid is cancerous, so the assays are not contaminated by wild-type mtDNA."
"We‘re in the process of obtaining DNA chips in hopes of vastly expanding our mtDNA library over the next year," he added.
The human mitochondrial DNA sequence can be examined at www.gen.emory.edu/mitomap.html., 百拇医药
High levels of mitochondrial DNA (mtDNA) are ubiquitous in human cells, the authors explain, and most copies of mtDNA are identical at birth. Furthermore, the entire gene sequence must be expressed to maintain proper mitochondrial function, "suggesting that even slight alterations in DNA sequences could have profound effects."
, http://www.100md.com
Dr. David Sidransky and colleagues from Johns Hopkins University School of Medicine in Baltimore, Maryland, analyzed 14 human bladder tumors, 13 head and neck tumors, and 14 lung primary tumors for mtDNA mutations and compared the results with mtDNA from samples of bodily fluids.
The scientists report their detection of 292 mtDNA sequence variations, 196 of which represented previously recorded polymorphisms and 57 of which were previously unknown polymorphisms. "The remaining 39 variants were acquired (somatic) mutations identified in 64%...of the bladder cancer patients, 46%...of the head and neck cancer patients, and 43%...of the lung cancer patients," the investigators note.
, 百拇医药
Mutant mtDNA derived from tumor tissues was found in all three urine samples obtained from patients with bladder cancer, in two thirds of the saliva samples from patients with head and neck cancer, and in 8 of 10 bronchoalveolar lavage samples from patients with lung cancer.
"In addition," the researchers report, "several of the bladder and head and neck cancers studied here had multiple mutations, implying possible accumulation of mtDNA damage."
, 百拇医药
A considerable number of the mtDNA mutations were localized in the displacement-loop (D-loop) region, a key site for both replication and expression of the mt genome, the results indicated.
"Although additional investigation is needed to define the functional importance of mt mutations, our data establish that these mutations are frequent and present at high levels in all of the tumor types examined," the authors conclude. "Because of its high copy number, mtDNA may provide a distinct advantage over other nuclear genome-based methods for cancer detection."
, 百拇医药
"With a mt genome that‘s only around 16 kb, it should be fairly straightforward to determine which mutations associate with which kinds of tumors," Dr. Sidransky told Reuters Health. "The whole process is also helped by the fact that virtually every cell that falls off into the body fluid is cancerous, so the assays are not contaminated by wild-type mtDNA."
"We‘re in the process of obtaining DNA chips in hopes of vastly expanding our mtDNA library over the next year," he added.
The human mitochondrial DNA sequence can be examined at www.gen.emory.edu/mitomap.html., 百拇医药