Journal ArticleDOI
Deciphering intratumor heterogeneity using cancer genome analysis.
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TLDR
The ability to identify and monitor the subclonal architecture of a tumor is valuable for the development of precise cancer therapeutic methods and single-cell sequencing will enable the identification of every minor population within a tumor microenvironment.Abstract:
Intratumor heterogeneity within individual cancer tissues underlies the numerous phenotypes of cancer. Tumor subclones ultimately affect therapeutic outcomes due to their distinct molecular features. Drug-resistant subclones are present at a low frequency in tissues at the time of biopsy, but can also arise as a result of acquired somatic mutations. A number of different approaches have been utilized to understand the nature of intratumor heterogeneity. Clonal analysis using whole exome or genome sequencing data can help monitor subclones in the context of tumor progression. Multiregional biopsies permit the molecular characterization of subclones within tumors. Deep sequencing has also provided researchers with the ability to measure the low allele fraction variant within a small number of cells. Ultimately, single-cell sequencing will enable the identification of every minor population within a tumor microenvironment. In the clinical context, the ability to identify and monitor the subclonal architecture of a tumor is valuable for the development of precise cancer therapeutic methods.read more
Citations
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The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy
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Intratumor heterogeneity inferred from targeted deep sequencing as a prognostic indicator
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References
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Journal ArticleDOI
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +30 more
TL;DR: Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development.
Journal ArticleDOI
American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer
M. Elizabeth H. Hammond,Daniel F. Hayes,Mitch Dowsett,D. Craig Allred,Karen L. Hagerty,Sunil V. Badve,Patrick L. Fitzgibbons,Glenn Francis,Neil S. Goldstein,Malcolm Hayes,David G. Hicks,Susan C. Lester,Richard Love,Pamela B. Mangu,Lisa M. McShane,Keith Miller,C. Kent Osborne,Soonmyung Paik,Jane Perlmutter,Anthony Rhodes,Hironobu Sasano,Jared N. Schwartz,Fred C.G.J. Sweep,Sheila E. Taube,Emina Torlakovic,Paul N. Valenstein,Giuseppe Viale,Daniel W. Visscher,Thomas M. Wheeler,R. Bruce Williams,James L. Wittliff,Antonio C. Wolff +31 more
TL;DR: An international Expert Panel that conducted a systematic review and evaluation of the literature and developed recommendations for optimal IHC ER/PgR testing performance recommended that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences.
Journal ArticleDOI
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Kristian Cibulskis,Michael S. Lawrence,Scott L. Carter,Andrey Sivachenko,David M. Jaffe,Carrie Sougnez,Stacey Gabriel,Matthew Meyerson,Matthew Meyerson,Eric S. Lander,Eric S. Lander,Eric S. Lander,Gad Getz,Gad Getz +13 more
TL;DR: The MuTect algorithm for calling somatic point mutations enables subclonal analysis of the whole-genome or whole-exome sequencing data being generated in large-scale cancer genomics projects as discussed by the authors.
Journal ArticleDOI
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Anoop P. Patel,Itay Tirosh,John J. Trombetta,Alex K. Shalek,Shawn M. Gillespie,Hiroaki Wakimoto,Daniel P. Cahill,Brian V. Nahed,William T. Curry,Robert L. Martuza,David N. Louis,Orit Rozenblatt-Rosen,Mario L. Suvà,Mario L. Suvà,Aviv Regev,Aviv Regev,Aviv Regev,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +19 more
TL;DR: The genome sequence of single cells isolated from brain glioblastomas was examined, which revealed shared chromosomal changes but also extensive transcription variation, including genes related to signaling, which represent potential therapeutic targets.
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Kristian Cibulskis,Andrey Sivachenko,David B. Jaffe,Carrie Sougnez,Stacey Gabriel,Matthew Meyerson,Gad Getz,Eric S. Lander,Michael S. Lawrence,Scott L. Carter +9 more
TL;DR: MuTect is presented, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity.
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