Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer
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Purpose The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients. Materials and Methods Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients. Results Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC. Conclusion Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.
Abstract
Purpose The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients. Materials and Methods Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients. Results Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC. Conclusion Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.
참고문헌 (29)
- Torre LA, "Ovarian cancer statistics, 2018", CA Cancer J Clin, 68, pp.284~296 (2018)
- Clarke-Pearson DL, "Clinical practice. Screening for ovarian cancer", N Engl J Med, 361, pp.170~177 (2009)
- Jayson GC, "Ovarian cancer", Lancet, 384, pp.1376~1388 (2014)
- Smolle E, "Malignant ascites in ovarian cancer and the role of targeted therapeutics", Anticancer Res, 34, pp.1553~1561 (2014)
- Ahmed N, "Getting to know ovarian cancer ascites : opportunities for targeted therapy-based translational research", Front Oncol, 3, pp.256~ (2013)
- Choi YJ, "Intraindividual genomic heterogeneity of high-grade serous carcinoma of the ovary and clinical utility of ascitic cancer cells for mutation profiling", J Pathol, 241, pp.57~66 (2017)
- Wan JC, "Liquid biopsies come of age : towards implementation of circulating tumour DNA", Nat Rev Cancer, 17, pp.223~238 (2017)
- Murtaza M, "Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA", Nature, 497, pp.108~112 (2013)
- Husain H, "Cell-free DNA from ascites and pleural effusions : molecular insights into genomic aberrations and disease biology", Mol Cancer Ther, 16, pp.948~955 (2017)
- Zhou S, "Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient", Cancer Biol Ther, 20, pp.15~20 (2019)
- Chen S, "fastp : an ultra-fast all-in-one FASTQ preprocessor", Bioinformatics, 34, pp.i884~90 (2018)
- "Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM"[URL]
- Li H, "The Sequence Alignment", Map format and SAMtools, 2009, pp.25, 2078~2079
- Cibulskis K, "Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples", Nat Biotechnol, 31, pp.213~219 (2013)
- Wang K, "ANNOVAR : functional annotation of genetic variants from high-throughput sequencing data", Nucleic Acids Res, 38, pp.e164~ (2010)
- Lee S, "Korean Variant Archive(KOVA) : a reference database of genetic variations in the Korean population", Sci Rep, 7, pp.4287~ (2017)
- Vaser R, "SIFT missense predictions for genomes", Nat Protoc, 11, pp.1~9 (2016)
- Choi Y, "PROVEAN web server : a tool to predict the functional effect of amino acid substitutions and indels", Bioinformatics, 31, pp.2745~2747 (2015)
- Zhang Y, "TP53 mutations in epithelial ovarian cancer", Transl Cancer Res, 5, pp.650~663 (2016)
- Levine DA, "Frequent mutation of the PIK3CA gene in ovarian and breast cancers", Clin Cancer Res, 11, pp.2875~2878 (2005)
- Zeng M, "Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12", 13, 2018, pp.7, e39030~
- Lheureux S, "Epithelial ovarian cancer", Lancet, 393, pp.1240~1253 (2019)
- Soletormos G, "Clinical use of cancer biomarkers in epithelial ovarian cancer : updated huidelines from the European group on tumor markers", Int J Gynecol Cancer, 26, pp.43~51 (2016)
- Kamat AA, "Plasma cell-free DNA in ovarian cancer : an independent prognostic biomarker", Cancer, 116, pp.1918~1925 (2010)
- Giannopoulou L, "Liquid biopsy in ovarian cancer : recent advances on circulating tumor cells and circulating tumor DNA", Clin Chem Lab Med, 56, pp.186~197 (2018)
- Parkinson CA, "Exploratory analysis of TP53 mutations in circulating tumour DNA as biomarkers of treatment response for patients with relapsed high-grade serous ovarian carcinoma : a retrospective study", PLoS Med, 13, pp.e1002198~ (2016)
- Cohen JD, "Detection and localization of surgically resectable cancers with a multi-analyte blood test", Science, 359, pp.926~930 (2018)
- Chen X, "Targeted resequencing of the microRNAome and 3'UTRome reveals functional germline DNA variants with altered prevalence in epithelial ovarian cancer", Oncogene, 34, pp.2125~2137 (2015)
- Evans DGR, "A dominantly inherited 5' UTR variant causing methylation-associated silencing of BRCA1 as a cause of breast and ovarian cancer", Am J Hum Genet, 103, pp.213~220 (2018)