Oncotarget

Research Papers:

Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay

Maria Schwaederle _, Hatim Husain, Paul T. Fanta, David E. Piccioni, Santosh Kesari, Richard B. Schwab, Kimberly C. Banks, Richard B. Lanman, AmirAli Talasaz, Barbara A. Parker and Razelle Kurzrock

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Oncotarget. 2016; 7:9707-9717. https://doi.org/10.18632/oncotarget.7110

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Abstract

Maria Schwaederle1, Hatim Husain1, Paul T. Fanta1, David E. Piccioni1, Santosh Kesari1, Richard B. Schwab1, Kimberly C. Banks2, Richard B. Lanman2, AmirAli Talasaz2, Barbara A. Parker1, Razelle Kurzrock1

1Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA

2Guardant Health, Inc., Redwood City, CA, USA

Correspondence to:

Maria Schwaederle, e-mail: [email protected]

Keywords: cancer, liquid biopsy, ctDNA, actionable alteration, personalized therapy

Received: September 30, 2015    Accepted: January 23, 2016    Published: February 01, 2016

ABSTRACT

Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent.


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