Development of personalized tumor biomarkers using massively parallel sequencing.
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.
Leary
Rebecca J
RJ
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
Kinde
Isaac
I
Diehl
Frank
F
Schmidt
Kerstin
K
Clouser
Chris
C
Duncan
Cisilya
C
Antipova
Alena
A
Lee
Clarence
C
McKernan
Kevin
K
De La Vega
Francisco M
FM
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Diaz
Luis A
LA
Velculescu
Victor E
VE
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
D014408:Biomarkers, Tumor; D004247:DNA