Monitoring response to therapy in melanoma by quantifying circulating tumour DNA with droplet digital PCR for BRAF and NRAS mutations

被引：138

作者：

Tsao, Simon Chang-Hao ^{[1
,2
]}

Weiss, Jonathan ^{[1
]}

Hudson, Christopher ^{[1
,4
]}

Christophi, Christopher ^{[2
]}

Cebon, Jonathan ^{[1
,3
,4
]}

Behren, Andreas ^{[1
,3
,4
]}

Dobrovic, Alexander ^{[1
,3
,4
]}

机构：

[1] Olivia Newton John Canc Res Inst, Heidelberg, Vic, Australia

[2] Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic, Australia

[3] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

[4] La Trobe Univ, Sch Canc Med, Bundoora, Vic, Australia

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

英国医学研究理事会;

关键词：

NUCLEIC-ACIDS; CANCER; PLASMA;

D O I：

10.1038/srep11198

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We assessed the utility of droplet digital PCR (ddPCR) to evaluate the potential of using circulating tumour DNA (ctDNA) as a post therapy monitoring tool in melanoma by comparing it to serum LDH levels and RECIST scores. ddPCR was shown to be reliable in distinguishing mutant from wild type alleles with no false positives. Subsequently, we quantified ctDNA ((V600)EBRAF, (V600)KBRAF or (Q61H)NRAS) in 6 stage IV melanoma patients across several time points during their treatment course. All tested patients had detectable ctDNA, which exhibited dynamic changes corresponding to the changes in their disease status. The ctDNA levels fell upon treatment response and rose with detectable disease progression. In our group of patients, ctDNA was more consistent and informative than LDH as a blood-based biomarker. In addition, BRAF mutant ctDNA as detected by ddPCR could be used diagnostically where the tumour block was unavailable. In conclusion, this study demonstrates the applicability of using ddPCR to detect and quantify ctDNA in the plasma of melanoma patients.

引用

页数：11

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