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01-12-2014 | Translational Research and Biomarkers

Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors

Authors: Jen-Kou Lin, MD, PhD, Pei-Ching Lin, MD, Chien-Hsing Lin, PhD, Jeng-Kai Jiang, MD, PhD, Shung-Haur Yang, MD, PhD, Wen-Yi Liang, MD, Wei-Shone Chen, MD, PhD, Shih-Ching Chang, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

Abstract

Background

While circulating plasma DNA (cpDNA) likely originates in tumors, its utility is limited without knowledge of tumor mutations. This study assessed mutational spectra in primary tumors and clarified the utility of quantitative and qualitative cpDNA alterations in colorectal cancer (CRC) patients.

Materials and Methods

Between 2005 and 2006, 191 surgical colorectal cancer patients at Taipei Veterans General Hospital were enrolled in a study of mutational spectra of 155 mutations in 74 genes. Concentrations of cpDNA in 133 patients were measured by Taqman qPCR. The measured endpoint was overall survival (OS) after surgery. The prognostic value was determined using the log-rank test and Cox regression analysis.

Results

Of 191 tumors, 208 mutations in 17 genes were found in 137 tumors (71.7 %). Mutation frequencies were 38.7 % in KRAS, followed by APC (23.0 %), TP53 (19.9 %), PIK3CA (7.3 %), and BRAF (4.2 %). The median cpDNA in stage I, II, and III patients was 4,300, 4,800, and 5,600 copies/mL, respectively, increasing to 13,000 copies/mL in stage IV disease (p = .003). From 90 primary tumors with mutations, the sensitivity of cpDNA mutations were 24.0, 45.0, and 27.3 % in the stage I, II, and III disease, respectively, increasing to 87.5 % in stage IV. The 5-year OS of CRC patients with low cpDNA was significantly better than that of patients with high cpDNA (p = .001). Stepwise elimination showed cpDNA to be a strong prognostic factor for OS.

Conclusions

Plasma DNA alteration is a useful tool for clinical surveillance of colorectal cancer patients and might be an independent prognosticator.

Available only for authorised users

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Title: Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors
Authors: Jen-Kou Lin, MD, PhD
Pei-Ching Lin, MD
Chien-Hsing Lin, PhD
Jeng-Kai Jiang, MD, PhD
Shung-Haur Yang, MD, PhD
Wen-Yi Liang, MD
Wei-Shone Chen, MD, PhD
Shih-Ching Chang, MD, PhD
Publication date: 01-12-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-014-3804-5

At a glance: The STEP trials

Springer Medicine

Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors

Abstract

Background

Materials and Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Materials and Methods

Results

Conclusions

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