title: Development of personalized tumor biomarkers using massively parallel sequencing.
abstract: Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers with massively parallel sequencing revealed an average of nine rearranged sequences (range, 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints was able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Leary
authors.forename: Isaac
authors.initials: I
authors.lastname: Kinde
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schmidt
authors.forename: Chris
authors.initials: C
authors.lastname: Clouser
authors.forename: Cisilya
authors.initials: C
authors.lastname: Duncan
authors.forename: Alena
authors.initials: A
authors.lastname: Antipova
authors.forename: Clarence
authors.initials: C
authors.lastname: Lee
authors.forename: Kevin
authors.initials: K
authors.lastname: McKernan
authors.forename: Francisco M
authors.initials: FM
authors.lastname: De La Vega
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D057285:Precision Medicine / Q000295:instrumentation / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA