title: Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nickerson
authors.forename: Jan F
authors.initials: JF
authors.lastname: Simons
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Torstein
authors.initials: T
authors.lastname: Tengs
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yuza
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.forename: Thomas
authors.initials: T
authors.lastname: LaFramboise
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lee
authors.forename: Kinjal
authors.initials: K
authors.lastname: Shah
authors.forename: Keith
authors.initials: K
authors.lastname: O'Neill
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Neal
authors.initials: N
authors.lastname: Lindeman
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Ana M
authors.initials: AM
authors.lastname: Borras
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gutmann
authors.forename: Konstantin H
authors.initials: KH
authors.lastname: Dragnev
authors.forename: Ralph
authors.initials: R
authors.lastname: DeBiasi
authors.forename: Tzu-Hsiu
authors.initials: TH
authors.lastname: Chen
authors.forename: Karen A
authors.initials: KA
authors.lastname: Glatt
authors.forename: Heidi
authors.initials: H
authors.lastname: Greulich
authors.forename: Brian
authors.initials: B
authors.lastname: Desany
authors.forename: Christine K
authors.initials: CK
authors.lastname: Lubeski
authors.forename: William
authors.initials: W
authors.lastname: Brockman
authors.forename: Pablo
authors.initials: P
authors.lastname: Alvarez
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Hutchison
authors.forename: J H
authors.initials: JH
authors.lastname: Leamon
authors.forename: Michael T
authors.initials: MT
authors.lastname: Ronan
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Turenchalk
authors.forename: Michael
authors.initials: M
authors.lastname: Egholm
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rothberg
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm