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Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing |
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| Authors: | Thomas Roman K Nickerson Elizabeth Simons Jan F Jänne Pasi A Tengs Torstein Yuza Yuki Garraway Levi A LaFramboise Thomas Lee Jeffrey C Shah Kinjal O'Neill Keith Sasaki Hidefumi Lindeman Neal Wong Kwok-Kin Borras Ana M Gutmann Edward J Dragnev Konstantin H DeBiasi Ralph Chen Tzu-Hsiu Glatt Karen A Greulich Heidi Desany Brian Lubeski Christine K Brockman William Alvarez Pablo Hutchison Stephen K Leamon J H Ronan Michael T Turenchalk Gregory S Egholm Michael Sellers William R Rothberg Jonathan M Meyerson Matthew |
| Institution: | Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA. |
| Abstract: | The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies. |
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