Title |
Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA
|
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Published in |
Science Translational Medicine, May 2012
|
DOI | 10.1126/scitranslmed.3003726 |
Pubmed ID | |
Authors |
Tim Forshew, Muhammed Murtaza, Christine Parkinson, Davina Gale, Dana W. Y. Tsui, Fiona Kaper, Sarah-Jane Dawson, Anna M. Piskorz, Mercedes Jimenez-Linan, David Bentley, James Hadfield, Andrew P. May, Carlos Caldas, James D. Brenton, Nitzan Rosenfeld |
Abstract |
Plasma of cancer patients contains cell-free tumor DNA that carries information on tumor mutations and tumor burden. Individual mutations have been probed using allele-specific assays, but sequencing of entire genes to detect cancer mutations in circulating DNA has not been demonstrated. We developed a method for tagged-amplicon deep sequencing (TAm-Seq) and screened 5995 genomic bases for low-frequency mutations. Using this method, we identified cancer mutations present in circulating DNA at allele frequencies as low as 2%, with sensitivity and specificity of >97%. We identified mutations throughout the tumor suppressor gene TP53 in circulating DNA from 46 plasma samples of advanced ovarian cancer patients. We demonstrated use of TAm-Seq to noninvasively identify the origin of metastatic relapse in a patient with multiple primary tumors. In another case, we identified in plasma an EGFR mutation not found in an initial ovarian biopsy. We further used TAm-Seq to monitor tumor dynamics, and tracked 10 concomitant mutations in plasma of a metastatic breast cancer patient over 16 months. This low-cost, high-throughput method could facilitate analysis of circulating DNA as a noninvasive "liquid biopsy" for personalized cancer genomics. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 11 | 28% |
Canada | 3 | 8% |
Japan | 2 | 5% |
United Kingdom | 2 | 5% |
France | 2 | 5% |
Germany | 1 | 3% |
Mexico | 1 | 3% |
Spain | 1 | 3% |
Belgium | 1 | 3% |
Other | 0 | 0% |
Unknown | 16 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 20 | 50% |
Scientists | 18 | 45% |
Practitioners (doctors, other healthcare professionals) | 2 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 13 | 1% |
United States | 12 | 1% |
Korea, Republic of | 3 | <1% |
Norway | 3 | <1% |
Netherlands | 2 | <1% |
Ireland | 2 | <1% |
Argentina | 2 | <1% |
Japan | 2 | <1% |
Canada | 2 | <1% |
Other | 8 | <1% |
Unknown | 1091 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 303 | 27% |
Student > Ph. D. Student | 213 | 19% |
Student > Master | 95 | 8% |
Other | 94 | 8% |
Student > Bachelor | 89 | 8% |
Other | 176 | 15% |
Unknown | 170 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 330 | 29% |
Medicine and Dentistry | 243 | 21% |
Biochemistry, Genetics and Molecular Biology | 239 | 21% |
Engineering | 22 | 2% |
Computer Science | 19 | 2% |
Other | 79 | 7% |
Unknown | 208 | 18% |