title: Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.
abstract: Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4].
authors.forename: Jens G
authors.initials: JG
authors.lastname: Lohr
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3].
authors.forename: Viktor A
authors.initials: VA
authors.lastname: Adalsteinsson
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2].
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Atish D
authors.initials: AD
authors.lastname: Choudhury
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cruz-Gordillo
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Francis
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Cheng-Zhong
authors.initials: CZ
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Alex K
authors.initials: AK
authors.lastname: Shalek
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Satija
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Trombetta
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Lu
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Naren
authors.initials: N
authors.lastname: Tallapragada
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Narmin
authors.initials: N
authors.lastname: Tahirova
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Sora
authors.initials: S
authors.lastname: Kim
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Blumenstiel
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Sougnez
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Alarice
authors.initials: A
authors.lastname: Lowe
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Bang
authors.initials: B
authors.lastname: Wong
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Auclair
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Eliezer M
authors.initials: EM
authors.lastname: Van Allen
authors.affiliation: 1] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Nakabayashi
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Rosina T
authors.initials: RT
authors.lastname: Lis
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Gwo-Shu M
authors.initials: GS
authors.lastname: Lee
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Li
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Chabot
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Ly
authors.affiliation: 1] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
authors.affiliation: 1] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Clancy
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: 1] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Jesse S
authors.identifier: 0000000267956336
authors.initials: JS
authors.lastname: Boehm
authors.affiliation: 1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Love
mesh_terms: D059472:Exome / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009360:Neoplastic Cells, Circulating; D011471:Prostatic Neoplasms / Q000235:genetics*
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