Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2010 Apr 8

PMID 20371490

Citations 245

Authors

Rebecca J Leary

Isaac Kinde

Frank Diehl

Kerstin Schmidt

Chris Clouser

Cisilya Duncan

Alena Antipova

Clarence Lee

Kevin McKernan

Francisco M De La Vega

Kenneth W Kinzler

Bert Vogelstein

Luis A Diaz Jr

Victor E Velculescu

Affiliations

Soon will be listed here.

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.

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