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

Author(s)

de Figueiredo Barros, Bruna D. ^[1] ; Kupper, Bruna E. C. ^[2] ; Aguiar Junior, Samuel ^[2] ; de Mello, Celso A. L. ^[3] ; Begnami, Maria D. ^[4] ; Chojniak, Rubens ^[5] ; de Souza, Sandro J. ^{[6, 7]} ; Torrezan, Giovana T. ^[1] ; Carraro, Dirce M. ^[1]

Affiliation

^[1] AC Camargo Canc Ctr, Lab Genom & Mol Biol, Int Res Ctr CIPE, Sao Paulo - Brazil

^[2] AC Camargo Canc Ctr, Colorectal Tumors Dept, Sao Paulo - Brazil

^[3] AC Camargo Canc Ctr, Clin Oncol Dept, Sao Paulo - Brazil

^[4] AC Camargo Canc Ctr, Dept Anat Pathol, Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Imaging Dept, Sao Paulo - Brazil

^[6] Univ Fed Rio Grande do Norte, Brain Inst, Natal, RN - Brazil

^[7] Univ Fed Rio Grande do Norte, Digital Metropolis Inst, Bioinformat Multidisciplinary Environm, Natal, RN - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 8, AUG 10 2018.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 13/23277-8 - Molecular aspects involved in the development and progression of breast ductal carcinoma: investigation of carcinoma in situ progression and the role of BRCA1 mutation in the triple negative tumor
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants