Diversity of circulating tumor cells in peripheral blood: Detection of heterogeneous BRAF mutations in a patient with advanced melanoma by single-cell analysis

Autor: Ryuhei Okuyama, Yasuyuki Akiyama, Kenta Nakamura, Atsushi Morimoto, Yukiko Kiniwa, Asuka Mikoshiba
Rok vydání: 2018
Předmět:
Zdroj: Journal of Dermatological Science. 90:211-213
ISSN: 0923-1811
DOI: 10.1016/j.jdermsci.2018.01.011
Popis: The advent of therapeutics targeting the MAPK signal pathway has led to great advances in the treatment of metastatic melanoma. However, a significant number of patients experience a short response and exhibit recurrence within several months after therapy, potentially related to mutation heterogeneity arising due to genetic and epigenetic instability of melanoma cells. Circulating tumor cells (CTCs) released from either primary or metastatic tumors are a non-invasive tool that could be used to characterise changes in tumors over time. However, the low concentrations of circulating tumor cells have significantly impeded the research necessary to evaluate their clinical utility. In this study, we demonstrated genetic heterogeneity in the BRAF V600 region in CTCs using a high-density dielectrophoretic microwell array, a novel rare-cell capture system. In a 77-year-old Japanese male, exon 15 of BRAF was wild-type in the primary lesion, BRAF K601E was detected in a metastatic lymph node. CTCs were defined as MART-1/gp100-positive and CD45-negative cells, and isolated by micromanipulation. Single-cell sequencing was performed in 33 CTCs: three contained BRAF K601E (one heterozygous and two homozygous mutations); two contained BRAF V600E (heterozygous); one contained BRAF V600A (heterozygous); and the remaining 27 CTCs were BRAF wild-type . This study indicates that CTCs are an important indicator of the potential for poor prognosis, treatment response, and disease recurrence.
Databáze: OpenAIRE
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