Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.

Roman K Thomas; Elizabeth Nickerson; Jan F Simons; Pasi A Jänne; Torstein Tengs; Yuki Yuza; Levi A Garraway; Thomas LaFramboise; Jeffrey C Lee; Kinjal Shah; Keith O'Neill; Hidefumi Sasaki; Neal Lindeman; Kwok-Kin Wong; Ana M Borras; Edward J Gutmann; Konstantin H Dragnev; Ralph DeBiasi; Tzu-Hsiu Chen; Karen A Glatt; Heidi Greulich; Brian Desany; Christine K Lubeski; William Brockman; Pablo Alvarez; Stephen K Hutchison; J H Leamon; Michael T Ronan; Gregory S Turenchalk; Michael Egholm; William R Sellers; Jonathan M Rothberg; Matthew Meyerson

doi:10.1038/nm1437

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Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.

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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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Base Sequence Chromosome Mapping DNA, Neoplasm Humans Molecular Sequence Data Mutation Neoplasms Sensitivity and Specificity Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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Roman K Thomas, Elizabeth Nickerson, Jan F Simons, Pasi A Jänne, Torstein Tengs, Yuki Yuza, Levi A Garraway, Thomas LaFramboise, Jeffrey C Lee, Kinjal Shah, Keith O'Neill, Hidefumi Sasaki, Neal Lindeman, Kwok-Kin Wong, Ana M Borras, Edward J Gutmann, Konstantin H Dragnev, Ralph DeBiasi, Tzu-Hsiu Chen, Karen A Glatt, Heidi Greulich, Brian Desany, Christine K Lubeski, William Brockman, Pablo Alvarez, Stephen K Hutchison, J H Leamon, Michael T Ronan, Gregory S Turenchalk, Michael Egholm, William R Sellers, Jonathan M Rothberg, Matthew Meyerson. 2006-06-25. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.. https://doi.org/10.1038/nm1437

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