Mutation analysis of BRAF and KIT in circulating melanoma cells at the single cell level

Sakaizawa, Kaori; Goto, Yasufumi; Kiniwa, Yukiko; Uchiyama, Aya; Harada, Kazutoshi; Shimada, Shinji; Saida, Toshiaki; Ferrone, Soldano; Takata, Minoru; Uhara, Hisashi; Okuyama, Ryuhei

doi:10.1038/bjc.2012.12

Cited by 94 publications

(71 citation statements)

References 45 publications

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“…BRAF has become one of the lead targets for therapy with specifi c inhibitors, and mutations in the BRAF gene are important predictors of sensitivity to therapy. Recently, dynamic changes of BRAF mutations were detected in CTCs and ctDNA ( 84,85 ), which may guide BRAF-directed therapies in the future.…”

Section: Dna Levelmentioning

confidence: 99%

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

2016

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ABSTRACT"Liquid biopsy" focusing on the analysis of circulating tumor cells (CTC) and circulating cell-free tumor DNA (ctDNA) in the blood of patients with cancer has received enormous attention because of its obvious clinical implications for personalized medicine. Analyses of CTCs and ctDNA have paved new diagnostic avenues and are, to date, the cornerstones of liquid biopsy diagnostics. The present review focuses on key areas of clinical applications of CTCs and ctDNA, including detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratifi cation of patients based on the detection of therapeutic targets or resistance mechanisms. Signifi cance:The application of CTCs and ctDNA for the early detection of cancer is of high public interest, but it faces serious challenges regarding specifi city and sensitivity of the current assays. Prediction of prognosis in patients with curable disease can already be achieved in several tumor entities, particularly in breast cancer. Monitoring the success or failure of systemic therapies (i.e., chemotherapy, hormonal therapy, or other targeted therapies) by sequential measurements of CTCs or ctDNA is also feasible. Interventional studies on treatment stratifi cation based on the analysis of CTCs and ctDNA are needed to implement liquid biopsy into personalized medicine. Cancer Discov; 6(5); 479-91.

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Section: Dna Levelmentioning

confidence: 99%

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

2016

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“…As metastatic lesions display unusual spindle cell morphology which lacks the common clinical and histological characteristics, the use of NG2/ CSPG4 in diagnosis could be potentially very useful. Collectively, NG2/ CSPG4 highly expresses in melanomas than normal tissues, suggesting that it would be a useful biomarker for melanoma [102][103][104][105] and more hope for treatment of this advanced cancer.…”

Section: Melanomamentioning

confidence: 99%

NG2/CSPG4 Proteoglycan as a Novel Prognostic Indicator and Therapeutic Target in Malignant Cancer

Bie¹

2014

J Stem Cell Res Ther

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This review article describes the interaction of Neuron-glia 2 Chondroitin Sulfate Proteoglycan 4 (NG2/CSPG4) in cancer cell matrix, and its role within the cancer cell matrix in promoting angiogenesis and its potential clinical use as a novel immune drug target. Malignant cancer is maintained by a cross-talk between the cancer cells and cancer cell matrix where the activated cancer cell matrix nurtures the advancing cancer cells by providing Extracellular Matrix (ECM), neovasculature and stimulatory growth factors. Researches in recent years have accumulated a wealth of novel insight into mechanisms by which how cancer cells are co-evolved with activated cancer cell matrix throughout cancer settings. Currently, the cancer cell matrix is considered as an important "effector" in carcinogenesis. Once tightly defined cell matrix in normal tissue occasionally becomes sabotaged, the inevitable malignant progression will flip on. NG2/CSPG4 is a big multifunctional transmembrane proteoglycan with limited expression in normal tissues and its unparalleled structural-functional diversity endows it with the ability to serve as critical mediator. We describe here how the manipulation of NG2/CSPG4 on the processes driving malignant cancer cell matrix activation promotes carcinogenesis through the alteration of cancer cell adhesion, infiltration, migration, proliferation and angiogenesis, and how it will be possibile to design a decisive strategy for the development of a novel therapy specifically targeting this macromolecule for malignant cancer treatment.

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“…BRAF V600E mutated DNA was detected in CTCs of 77% of melanoma patients with recorded mutated tumor tissues (14). In colorectal cancer, a report before showed that among 23 matched CTCs and ctDNA samples, the concordance was 73.9% for BRAF mutations (15). But the disadvantage of CTCs is that the repetitive rate and the success rate of PCR in CTCs were really low in the detection of BRAF mutations (14,16).…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of BRAFV600E mutation in circulating tumor DNA in Chinese patients with melanoma

Tang

Kong

et al. 2017

Oncol Lett

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Abstract. The present study aimed to assess the B rapidly accelerated fibrosarcoma (BRAF V600E ) status in plasma from Chinese patients with melanoma, and evaluated its prognostic value following treatment with BRAF inhibitors. Mutation-specific 3D digital polymerase chain reaction (dPCR) was used to quantify BRAF V600E in circulating tumor DNA (ctDNA) in 58 patients with melanoma, prior to treatment with BRAF inhibitors. Correlations between baseline ctDNA levels and clinicopathological characteristics and clinical benefits were then statistically analyzed. The concordance and sensitivity of BRAF V600E between ctDNA and tumor tissue were 70.2% and 76%, respectively, in 58 patients with melanoma. BRAF V600E mutation in ctDNA correlated with lactate dehydrogenase concentration (P= 0.04) and Eastern Cooperative Oncology Group score (P= 0.04). There was no correlation between BRAF V600E of ctDNA with response, progression-free survival (PFS), or overall survival (OS) following targeted therapy. The objective response rate, PFS and OS stratified by BRAF V600E of ctDNA were 30.0% vs. 56.7%, (P= 0.3), 8.1 months vs. 6.7 months, (P= 0.38) and 65.6 months vs. 42.3 months (P= 0.52), respectively, for undetectable and mutant types. In conclusion, 3D dPCR is appropriate for ctDNA detection and BRAF V600E in ctDNA is a non-invasive biomarker in patients with melanoma.

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Mutation analysis of BRAF and KIT in circulating melanoma cells at the single cell level

Cited by 94 publications

References 45 publications

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

NG2/CSPG4 Proteoglycan as a Novel Prognostic Indicator and Therapeutic Target in Malignant Cancer

Clinical significance of BRAFV600E mutation in circulating tumor DNA in Chinese patients with melanoma

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