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Front Oncol. 2018 Aug 10;8:306. doi: 10.3389/fonc.2018.00306. eCollection 2018.

Mutation Detection in Tumor-Derived Cell Free DNA Anticipates Progression in a Patient With Metastatic Colorectal Cancer.

Author information

1
Laboratory of Genomics and Molecular Biology-International Research Center/CIPE, A. C. Camargo Cancer Center, São Paulo, Brazil.
2
Colorectal Tumors Department, A. C. Camargo Cancer Center, São Paulo, Brazil.
3
Clinical Oncology Department, A. C. Camargo Cancer Center, São Paulo, Brazil.
4
Department of Anatomic Pathology, A. C. Camargo Cancer Center, São Paulo, Brazil.
5
Imaging Department, A. C. Camargo Cancer Center, São Paulo, Brazil.
6
Bioinformatics Multidisciplinary Environment, Digital Metropolis Institute, Federal University of Rio Grande do Norte, Natal, Brazil.
7
Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil.

Abstract

Background: The observation of tumor-derived cell-free DNA (ctDNA) in plasma brought new expectations to monitor treatment response in cancer patients. Case presentation: In an exploratory case of a 57-year-old man diagnosed with metastatic sigmoid adenocarcinoma, we used a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis.

RESULTS:

Five mutations were detected (KRAS, p.Gly12Val; TP53, p.Arg175His; RB1, p.Ile680Thr; ALK, p.Gly1184Glu; and ERBB2, p.Lys860Lys), of which three were detected in both tissue types (primary tumor and metastasis). All five mutations were monitored in the ctDNA of six serial plasma samples. Only KRAS and TP53 mutations were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy the allele frequencies of both mutations fell below the detection limit. From the third month of systemic treatment onward, the allele frequencies of both mutations were detectable in plasma, displaying a continual increase thereafter. The remaining three mutations were not detected in plasma samples. Signs of disease progression in ctDNA during the treatment period were evident while computed tomography (CT) measurements suggested stable metastatic lesions throughout the treatment. Conclusions: Liquid biopsies revealed tumor heterogeneity and predicted tumor progression, demonstrating the potential of ctDNA analysis to be a sensitive and specific tool for monitoring treatment responsivity and for early identification of treatment resistance.

KEYWORDS:

NGS; colorectal cancer; ctDNA; gene panel; liquid biopsy

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