Nature Medicine
- 12, 852 - 855 (2006)
Published online: 25 June 2006; Corrected online: 13 September 2006 | doi:10.1038/nm1437
There is an Erratum (October 2006) associated with this Technical Report.
Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencingRoman K Thomas1, 2, 12, Elizabeth Nickerson3, 12, Jan F Simons3, 11, 12, Pasi A Jänne1, Torstein Tengs1, 2, Yuki Yuza1, Levi A Garraway1, 2, 4, Thomas LaFramboise1, 2, Jeffrey C Lee1, 2, Kinjal Shah1, 2, Keith O'Neill2, Hidefumi Sasaki5, Neal Lindeman6, Kwok-Kin Wong1, Ana M Borras7, Edward J Gutmann8, Konstantin H Dragnev9, Ralph DeBiasi1, 2, Tzu-Hsiu Chen1, 2, Karen A Glatt1, Heidi Greulich1, 2, Brian Desany3, Christine K Lubeski3, William Brockman2, Pablo Alvarez2, Stephen K Hutchison3, J H Leamon3, Michael T Ronan3, Gregory S Turenchalk3, Michael Egholm3, William R Sellers1, 2, Jonathan M Rothberg3 & Matthew Meyerson1, 2, 10, 111
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA. 2
The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. 3
454 Life Sciences, 20 Commercial Street, Branford, Connecticut 06405, USA. 4
Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA. 5
Department of Surgery 2, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. 6
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. 7
Translational Research Laboratory, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA. 8
Department of Pathology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, New Hampshire 03756, USA. 9
Hematology/Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, New Hampshire 03756, USA. 10
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. 11
Center for Cancer Genome Discovery, Dana-Farber Cancer Institue, 44 Binney Street, Boston, Massachusetts 02115, USA. 12
These authors contributed equally to this work.
Correspondence should be addressed to Matthew Meyerson matthew_meyerson@dfci.harvard.edu 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.
NOTE: In the version of this article initially published, it should have been acknowledged that Jan F. Simons, in addition to Roman K. Thomas and Elizabeth Nickerson, contributed equally to this work. The error has been corrected in the HTML and PDF versions of the article.
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