Journal
BRITISH JOURNAL OF CANCER
Volume 106, Issue 5, Pages 939-946Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.12
Keywords
melanoma; circulating tumour cells; oncogene mutations; BRAF; KIT; HMW-MAA
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of the Japanese government
- Ministry of Health, Labor, and Welfare of Japan
- Japan Society for the Promotion of Science
- PHS [R01 CA138188]
- National Cancer Institute
- Grants-in-Aid for Scientific Research [21591429, 23591614, 23591615] Funding Source: KAKEN
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BACKGROUND: The availability of molecular-targeted therapies for the treatment of melanoma has emphasised the need to identify mutations in target genes such as BRAF and KIT. Circulating tumour cells (CTC) are present in the peripheral blood of a significant proportion of cancer patients. METHODS: High molecular weight melanoma-associated antigen (HMW-MAA) was used to isolate melanoma cells from peripheral blood as it is selectively expressed at high levels on melanomas. The HMW-MAA-positive cells were isolated using immunomagnetic beads. After removing CD45(+) cells, CTC were identified by staining with MART-1-and gp100-specific antibodies (HMW-MAA(+), CD45(-), MART-1/gp100(+)). Single, isolated CTC were then subjected to BRAF and KIT mutational analysis. RESULTS: CTC (HMW-MAA(+), CD45(-), MART-1/gp100(+)) were isolated from the blood of 11 patients and BRAF and KIT were sequenced in nine and four patients, respectively. The BRAF sequences identified in the CTC were inconsistent with those identified in autologous melanoma tumours in three patients and the KIT sequences were inconsistent in three patients. In addition, polyclonal BRAF mutations were identified in one patient and concomitant mutations in BRAF and KIT were identified in another patient. CONCLUSION: Melanoma cells show clonal heterogeneity. Therefore, CTC genotyping may be crucial for successful molecular-targeted therapy. British Journal of Cancer (2012) 106, 939-946. doi:10.1038/bjc.2012.12 www.bjcancer.com Published online 26 January 2012 (C) 2012 Cancer Research UK
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