Circulating Cell-Free DNA or Circulating Tumor DNA in the Management of Ovarian and Endometrial Cancer

Figures & data

Table 1 Studies with Analysis of cfDNA/ctDNA in OC or EC Patients

References	Country	Cancer Type	Sources	Cancer/Control	Abnormalities	Methodology	Clinical Relevance
Shao et al^Citation34	China	OC	Serum	36/41	Level	bDNA technique	Diagnosis
Kamat et al^Citation35	USA	OC	Plasma	164/124	Level	RT-PCR	Diagnosis
Kamat et al^Citation36	USA	OC	Plasma	19/12	Level	RT-PCR	Diagnosis
Zachariah et al^Citation37	Switzerland	OC	Serum/plasma	21/83	Level	RT-PCR	Diagnosis
Dobrzycka et al^Citation38	Poland	OC	Plasma	126/NA	Level/KRAS mutation	PCR-RFLP	Diagnosis/prognosis
Cicchillitti et al^Citation39	Italy	EC	seRum	59/NA	Level	RT-PCR	Diagnosis
Dobrzycka et al^Citation40	Poland	EC	Plasma	109/NA	Level	PCR-RFLP	Diagnosis
Vizza et al^Citation41	Italy	EC	Serum	60/NA	Level	RT-PCR	Diagnosis
Tanaka et al^Citation42	Japan	EC	Plasma	53/24	Level	RT-PCR	Diagnosis/prognosis
Hickey et al^Citation43	United Kingdom	OC	Serum	20/NA	Mutations, LOH and MI	PCR	Diagnosis
Otsuka et al^Citation46	Japan	OC	Plasma	27/NA	p53 mutation	PCR	Diagnosis/prognosis
Park et al^Citation47	Korea	OC	Plasma	4/NA	TP53 mutation	Digital PCR	Diagnosis
Cohen et al^Citation49	Australia	OC	Plasma	32/32	Chromosomal instability	Whole genome NIPT platform	Diagnosis
Vanderstichele et al^Citation50	Belgium	OC	Plasma	57/11	Chromosomal instability	NGS	Diagnosis
Phallen et al^Citation51	USA	OC	Plasma	42/NA	Somatic mutations	TEC-Seq	Diagnosis
Farkkila et al^Citation52	Finland	OC	Plasma	35/NA	FOXL2 mutation	ddPCR	Diagnosis/prognosis
Sun et al^Citation53	China	EC	PBLs	139/139	mtDNA copy number value	RT-PCR	Diagnosis
Giannopoulou et al^Citation56	Greece	OC	Plasma	59/NA	RASSF1A methylation	MSP technique	Diagnosis
Zhang et al^Citation57	China	OC	Serum	87/115	(APC, RASSF1A, CDH1, RUNX3, TFPI2, SFRP5, OPCML) methylation	MSP technique	Diagnosis
Liggett et al^Citation58	USA	OC	Plasma	30/60	(RASSF1A, CALCA, EP300, BRCA1, CDKN1C, PGR-PROX) methylation	MethDet 56	Diagnosis
Melnikov et al^Citation59	USA	OC	Plasma	33/33	(BRCA1, HIC1, PAX5, PGR, THBS1) methylation	MethDet 56	Diagnosis
Widschwendter et al^Citation60	UK	OC	Serum	25/598	(COL23A1, C2CD4D, WNT6) methylation	NGS	Diagnosis/prognosis
Li et al^Citation61	China	OC	Peripheral blood	206/205	Methylation at multiple sites	NGS	Diagnosis
Wu et al^Citation62	China	OC	Plasma	47/24	RASSF2A methylation	MSP technique	Diagnosis
Ibanez et al^Citation63	USA	OC	Serum/plasma	50/NA	(BRCA1, RASSF1A) methylation	MSP technique	Diagnosis
Margolin et al^Citation67	USA	EC	A computational simulation	42/8	ZNF154 methylation	NGS	Diagnosis
Wimberger et al^Citation71	Germany	OC	plasma	62/28	Level	RT-PCR	prognosis
Perkins et al^Citation72	United Kingdom	OC	Plasma	105/20	Level/mutations in 19 genes	NGS	Prognosis
Steffensen et al^Citation73	Denmark	OC	Plasma	144/NA	Level	RT-PCR	Prognosis
No et al^Citation74	Korea	OC	Plasma	36/16	(B2M, RAB25, CLDN4, ABCF2) mutation	RT-PCR	Prognosis
Kuhlmann et al^Citation75	Germany	OC	Serum	63/20	Level/LOH	Fluorescence-labeled PCR	Prognosis
Swisher et al^Citation48	USA	OC	Plasma/serum	137/NA	p53 mutation	DNA sequencing	Prognosis
Giannopoulou et al^Citation76	Greece	OC	Plasma	129/NA	ESR1 methylation	MSP technique	Prognosis
Bolivar et al^Citation70	USA	EC	Plasma	48/NA	(CTNNB1, KRAS, PTEN, PIK3CA) mutation	NGS	Prognosis
Harris et al^Citation77	USA	OC	Plasma	8/NA	Chromosomal junctions	Quantitative PCR	Prognosis
Pereira et al^Citation78	USA	OC and EC	Serum	22OC,17EC/NA	Level	Digital PCR	Prognosis
Du et al^Citation79	China	OC	Plasma	21/NA	Mutations/CNV	NGS	Prognosis
Martignetti et al^Citation80	USA	OC	Plasma/serum	1/NA	FGFR fusions	NGS/RT-PCR	Prognosis
Choudhuri et al^Citation82	India	OC	Plasma	100/NA	Level	RT-PCR	Treatment response
Capizzi et al^Citation83	Italy	OC	Plasma	22/NA	Level	RT-PCR	Treatment response
Arend et al^Citation84	USA	OC	plasma	14/NA	level	NGS	Treatment response
Kamat et al^Citation69	USA	OC in mice	Plasma	–	Level	RT-PCR	Treatment response
Parkinson et al^Citation68	United Kingdom	OC	Plasma	40/NA	TP53 mutation	Digital PCR	Treatment response
Gifford et al^Citation85	United Kingdom	OC	Plasma	138/NA	hMLH1 methylation	Microsatellite PCR	Treatment response
Flanagan et al^Citation86	United Kingdom	OC	Peripheral blood	247/NA	Methylation at CpG sites	NGS	Treatment response
Matulonis et al^Citation90	USA	OC	Plasma	67/NA	Mutations in components/modulators of the PI3K pathway	NGS/Sanger sequencing	Treatment response
Weigelt et al^Citation87	USA	OC	Plasma	19/NA	BRCA reversion mutation	NGS	Treatment response
Christie et al^Citation88	Australia	OC	Plasma	30/NA	BRCA reversion mutation	NGS	Treatment response
Lin et al^Citation89	USA	OC	Plasma	209/NA	BRCA reversion mutation	NGS	Treatment response

Abbreviations: OC, ovarian cancer; EC, endometrial cancer; bDNA, branched DNA; PCR-RFLP, PCR-restriction fragment length polymorphism; LOH, loss of heterozygosity; MI, microsatellite instability; NGS, next-generation sequencing; mtDNA, mitochondrial DNA; ddPCR, digital droplet PCR; PBLs, peripheral blood leukocytes; MSP, methylation-specific PCR; CNV, copy number variation; NK, do not know.

Figure 1 Applications of cfDNA/ctDNA in ovarian or endometrial cancer patients. 

Table 2 Studies with Analysis of cfDNA/ctDNA in Other Body Fluids of OC or EC Patients

References	Country	Cancer Type	Fluid Type	Number of Samples	Abnormalities	Methodology	Clinical Relevance
Hickey et al^Citation43	United Kingdom	OC	Peritoneal fluid	20	Mutations, LOH and MI	PCR	Diagnosis
Swisher et al^Citation48	USA	OC	Peritoneal fluid	30	p53 mutation	DNA sequencing	Prognosis
Krimmel et al^Citation104	USA	OC	Peritoneal fluid	37	TP53 mutation	Duplex sequencing	Diagnosis
Parrella et al^Citation105	Italy	OC	Peritoneal fluid	15	(p53,KRAS) mutation/LOH	DNA sequencing	Diagnosis
Barquin et al^Citation106	Spain	OC	Peritoneal fluid	10	BRCA mutation	DNA sequencing	Prognosis
Muller et al^Citation107	Austria	OC	Peritoneal fluid	61	methylation of 15 selected genes	MethyLight	Prognosis
Ibanez et al^Citation63	USA	OC	Peritoneal fluid	42	(BRCA1, RASSF1A) methylation	MSP technique	Diagnosis
Du et al^Citation79	China	OC	Urine and ascites	21 and 13	Mutations/CNV	NGS	Prognosis
Nair et al^Citation108	USA	EC	Uterine lavage fluid	107	Mutations of selected genes	NGS	Diagnosis
Maritschnegg et al^Citation109	Austria	OC and EC	Uterine lavage fluid	30 and 5	Somatic mutations	NGS	Diagnosis
Kinde et al^Citation110	USA	OC and EC	Liquid-based Pap smear	22and 24	Somatic mutations	NGS	Diagnosis
Wang et al^Citation111	USA	OC and EC	Pap brush samples	245 and 382	Somatic mutation	Safe-sequencing system	Diagnosis

Abbreviations: OC, ovarian cancer; EC, endometrial cancer; LOH, loss of heterozygosity; MI, microsatellite instability; MSP, methylation-specific PCR; CNV, copy number variation; NGS, next-generation sequencing; Pap, Papanicolaou.

Shao X, He Y, Ji M, et al. Quantitative analysis of cell-free DNA in ovarian cancer. Oncol Lett. 2015;10(6):3478–3482. doi:10.3892/ol.2015.377126788153

 PubMed Web of Science ®Google Scholar

Kamat AA, Baldwin M, Urbauer D, et al. Plasma cell-free DNA in ovarian cancer: an independent prognostic biomarker. Cancer. 2010;116(8):1918–1925. doi:10.1002/cncr.v116:820166213

 PubMed Web of Science ®Google Scholar

Kamat AA, Sood AK, Dang D, Gershenson DM, Simpson JL, Bischoff FZ. Quantification of total plasma cell-free DNA in ovarian cancer using real-time PCR. Ann N Y Acad Sci. 2006;1075:230–234. doi:10.1196/annals.1368.03117108216

 PubMed Web of Science ®Google Scholar

Zachariah RR, Schmid S, Buerki N, Radpour R, Holzgreve W, Zhong X. Levels of circulating cell-free nuclear and mitochondrial DNA in benign and malignant ovarian tumors. Obstet Gynecol. 2008;112(4):843–850. doi:10.1097/AOG.0b013e3181867bc018827127

 PubMed Web of Science ®Google Scholar

Dobrzycka B, Terlikowski SJ, Kinalski M, Kowalczuk O, Niklinska W, Chyczewski L. Circulating free DNA and p53 antibodies in plasma of patients with ovarian epithelial cancers. Ann Oncol. 2011;22(5):1133–1140. doi:10.1093/annonc/mdq58421098618

 PubMed Web of Science ®Google Scholar

Cicchillitti L, Corrado G, De Angeli M, et al. Circulating cell-free DNA content as blood based biomarker in endometrial cancer. Oncotarget. 2017;8(70):115230–115243. doi:10.18632/oncotarget.v8i7029383155

 PubMedGoogle Scholar

Dobrzycka B, Terlikowski SJ, Mazurek A, et al. Circulating free DNA, p53 antibody and mutations of KRAS gene in endometrial cancer. Int J Cancer. 2010;127(3):612–621. doi:10.1002/ijc.v127:319960433

 PubMed Web of Science ®Google Scholar

Vizza E, Corrado G, De Angeli M, et al. Serum DNA integrity index as a potential molecular biomarker in endometrial cancer. J Exp Clin Cancer Res. 2018;37(1):16. doi:10.1186/s13046-018-0688-429382392

 PubMedGoogle Scholar

Tanaka H, Tsuda H, Nishimura S, et al. Role of circulating free alu DNA in endometrial cancer. Int J Gynecol Cancer. 2012;22(1):82–86. doi:10.1097/IGC.0b013e3182328c9422146763

 PubMed Web of Science ®Google Scholar

Hickey KP, Boyle KP, Jepps HM, Andrew AC, Buxton EJ, Burns PA. Molecular detection of tumour DNA in serum and peritoneal fluid from ovarian cancer patients. Br J Cancer. 1999;80(11):1803–1808. doi:10.1038/sj.bjc.669060110468300

 PubMed Web of Science ®Google Scholar

Otsuka J, Okuda T, Sekizawa A, et al. Detection of p53 mutations in the plasma DNA of patients with ovarian cancer. Int J Gynecol Cancer. 2004;14(3):459–464. doi:10.1111/ijg.2004.14.issue-315228418

 PubMed Web of Science ®Google Scholar

Park YR, Kim YM, Lee SW, et al. Optimization to detect TP53 mutations in circulating cell-free tumor DNA from patients with serous epithelial ovarian cancer. Obstet Gynecol Sci. 2018;61(3):328–336. doi:10.5468/ogs.2018.61.3.32829780774

 PubMedGoogle Scholar

Cohen PA, Flowers N, Tong S, Hannan N, Pertile MD, Hui L. Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening. BMC Med. 2016;14(1):126. doi:10.1186/s12916-016-0667-627558279

 PubMed Web of Science ®Google Scholar

Vanderstichele A, Busschaert P, Smeets D, et al. Chromosomal instability in cell-free DNA as a highly specific biomarker for detection of ovarian cancer in women with adnexal masses. Clin Cancer Res. 2017;23(9):2223–2231. doi:10.1158/1078-0432.CCR-16-107827852697

 PubMed Web of Science ®Google Scholar

Phallen J, Sausen M, Adleff V, et al. Direct detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017;9(403). doi:10.1126/scitranslmed.aan2415

 PubMed Web of Science ®Google Scholar

Farkkila A, McConechy MK, Yang W, et al. FOXL2 402C>G mutation can be identified in the circulating tumor DNA of patients with adult-type granulosa cell tumor. J Mol Diagn. 2017;19(1):126–136. doi:10.1016/j.jmoldx.2016.08.00527810330

 PubMed Web of Science ®Google Scholar

Sun Y, Zhang L, Ho SS, Wu X, Gu J. Lower mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of endometrial cancer. Mol Carcinog. 2016;55(6):1111–1117. doi:10.1002/mc.v55.626258624

 PubMed Web of Science ®Google Scholar

Giannopoulou L, Chebouti I, Pavlakis K, Kasimir-Bauer S, Lianidou ES. RASSF1A promoter methylation in high-grade serous ovarian cancer: a direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA. Oncotarget. 2017;8(13):21429–21443. doi:10.18632/oncotarget.v8i1328206954

 PubMed Web of Science ®Google Scholar

Zhang Q, Hu G, Yang Q, et al. A multiplex methylation-specific PCR assay for the detection of early-stage ovarian cancer using cell-free serum DNA. Gynecol Oncol. 2013;130(1):132–139. doi:10.1016/j.ygyno.2013.04.04823623832

 PubMed Web of Science ®Google Scholar

Liggett TE, Melnikov A, Yi Q, et al. Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors. Gynecol Oncol. 2011;120(1):113–120. doi:10.1016/j.ygyno.2010.09.01921056906

 PubMed Web of Science ®Google Scholar

Melnikov A, Scholtens D, Godwin A, Levenson V. Differential methylation profile of ovarian cancer in tissues and plasma. J Mol Diagn. 2009;11(1):60–65. doi:10.2353/jmoldx.2009.08007219074590

 PubMed Web of Science ®Google Scholar

Widschwendter M, Zikan M, Wahl B, et al. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer. Genome Med. 2017;9(1):116. doi:10.1186/s13073-017-0500-729268796

 PubMedGoogle Scholar

Li L, Zheng H, Huang Y, et al. DNA methylation signatures and coagulation factors in the peripheral blood leucocytes of epithelial ovarian cancer. Carcinogenesis. 2017;38(8):797–805. doi:10.1093/carcin/bgx05728637314

 PubMed Web of Science ®Google Scholar

Wu Y, Zhang X, Lin L, Ma XP, Ma YC, Liu PS. Aberrant methylation of RASSF2A in tumors and plasma of patients with epithelial ovarian cancer. Asian Pac J Cancer Prev. 2014;15(3):1171–1176. doi:10.7314/APJCP.2014.15.3.117124606436

 PubMedGoogle Scholar

Ibanez de Caceres I, Battagli C, Esteller M, et al. Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Cancer Res. 2004;64(18):6476–6481. doi:10.1158/0008-5472.CAN-04-152915374957

 PubMed Web of Science ®Google Scholar

Margolin G, Petrykowska HM, Jameel N, Bell DW, Young AC, Elnitski L. Robust detection of DNA hypermethylation of ZNF154 as a pan-cancer locus with in silico modeling for blood-based diagnostic development. J Mol Diagn. 2016;18(2):283–298. doi:10.1016/j.jmoldx.2015.11.00426857064

 PubMed Web of Science ®Google Scholar

Wimberger P, Roth C, Pantel K, Kasimir-Bauer S, Kimmig R, Schwarzenbach H. Impact of platinum-based chemotherapy on circulating nucleic acid levels, protease activities in blood and disseminated tumor cells in bone marrow of ovarian cancer patients. Int J Cancer. 2011;128(11):2572–2580. doi:10.1002/ijc.v128.1120715113

 PubMed Web of Science ®Google Scholar

Perkins G, Yap TA, Pope L, et al. Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers. PLoS One. 2012;7(11):e47020. doi:10.1371/journal.pone.004702023144797

 PubMed Web of Science ®Google Scholar

Steffensen KD, Madsen CV, Andersen RF, Waldstrom M, Adimi P, Jakobsen A. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab. Eur J Cancer. 2014;50(15):2611–2618. doi:10.1016/j.ejca.2014.06.02225087181

 PubMed Web of Science ®Google Scholar

No JH, Kim K, Park KH, Kim YB. Cell-free DNA level as a prognostic biomarker for epithelial ovarian cancer. Anticancer Res. 2012;32(8):3467–3471.22843932

 PubMed Web of Science ®Google Scholar

Kuhlmann JD, Schwarzenbach H, Wimberger P, Poetsch M, Kimmig R, Kasimir-Bauer S. LOH at 6q and 10q in fractionated circulating DNA of ovarian cancer patients is predictive for tumor cell spread and overall survival. BMC Cancer. 2012;12:325. doi:10.1186/1471-2407-12-32522849543

 PubMed Web of Science ®Google Scholar

Swisher EM, Wollan M, Mahtani SM, et al. Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. Am J Obstet Gynecol. 2005;193(3 Pt 1):662–667. doi:10.1016/j.ajog.2005.01.05416150257

 PubMed Web of Science ®Google Scholar

Giannopoulou L, Mastoraki S, Buderath P, et al. ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer. Gynecol Oncol. 2018;150(2):355–360. doi:10.1016/j.ygyno.2018.05.02629807696

 PubMed Web of Science ®Google Scholar

Bolivar AM, Luthra R, Mehrotra M, et al. Targeted next-generation sequencing of endometrial cancer and matched circulating tumor DNA: identification of plasma-based, tumor-associated mutations in early stage patients. Modern Pathol. 2019;32(3):405–414. doi:10.1038/s41379-018-0158-8

 PubMed Web of Science ®Google Scholar

Harris FR, Kovtun IV, Smadbeck J, et al. Quantification of somatic chromosomal rearrangements in circulating cell-free DNA from ovarian cancers. Sci Rep. 2016;6:29831. doi:10.1038/srep2983127436510

 PubMed Web of Science ®Google Scholar

Pereira E, Camacho-Vanegas O, Anand S, et al. Personalized circulating tumor DNA biomarkers dynamically predict treatment response and survival in gynecologic cancers. PLoS One. 2015;10(12):e0145754. doi:10.1371/journal.pone.014575426717006

 PubMed Web of Science ®Google Scholar

Du ZH, Bi FF, Wang L, Yang Q. Next-generation sequencing unravels extensive genetic alteration in recurrent ovarian cancer and unique genetic changes in drug-resistant recurrent ovarian cancer. Mol Genet Genomic Med. 2018. doi:10.1002/mgg3.414

 Web of Science ®Google Scholar

Martignetti JA, Camacho-Vanegas O, Priedigkeit N, et al. Personalized ovarian cancer disease surveillance and detection of candidate therapeutic drug target in circulating tumor DNA. Neoplasia. 2014;16(1):97–103. doi:10.1593/neo.13190024563622

 PubMed Web of Science ®Google Scholar

Choudhuri S, Sharma C, Banerjee A, Kumar S, Kumar L, Singh N. A repertoire of biomarkers helps in detection and assessment of therapeutic response in epithelial ovarian cancer. Mol Cell Biochem. 2014;386(1–2):259–269. doi:10.1007/s11010-013-1863-824141793

 PubMed Web of Science ®Google Scholar

Capizzi E, Gabusi E, Grigioni AD, et al. Quantification of free plasma DNA before and after chemotherapy in patients with advanced epithelial ovarian cancer. Diagn Mol Pathol. 2008;17(1):34–38. doi:10.1097/PDM.0b013e3181359e1f18303408

 PubMedGoogle Scholar

Arend RC, Londono AI, Montgomery AM, et al. Molecular response to neoadjuvant chemotherapy in high-grade serous ovarian carcinoma. Mol Cancer Res. 2018;16(5):813–824. doi:10.1158/1541-7786.MCR-17-059429523763

 PubMed Web of Science ®Google Scholar

Kamat AA, Bischoff FZ, Dang D, et al. Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian carcinoma. Cancer Biol Ther. 2006;5(10):1369–1374. doi:10.4161/cbt.5.10.324016969071

 PubMed Web of Science ®Google Scholar

Parkinson CA, Gale D, Piskorz AM, et al. 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. 2016;13(12):e1002198. doi:10.1371/journal.pmed.100219827997533

 PubMed Web of Science ®Google Scholar

Gifford G, Paul J, Vasey PA, Kaye SB, Brown R. The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. Clin Cancer Res. 2004;10(13):4420–4426. doi:10.1158/1078-0432.CCR-03-073215240532

 PubMed Web of Science ®Google Scholar

Flanagan JM, Wilson A, Koo C, et al. Platinum-based chemotherapy induces methylation changes in blood DNA associated with overall survival in patients with ovarian cancer. Clin Cancer Res. 2017;23(9):2213–2222. doi:10.1158/1078-0432.CCR-16-175427663594

 PubMed Web of Science ®Google Scholar

Matulonis U, Vergote I, Backes F, et al. Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. Gynecol Oncol. 2015;136(2):246–253. doi:10.1016/j.ygyno.2014.12.01925528496

 PubMed Web of Science ®Google Scholar

Weigelt B, Comino-Mendez I, de Bruijn I, et al. Diverse BRCA1 and BRCA2 reversion mutations in circulating cell-free DNA of therapy-resistant breast or ovarian cancer. Clin Cancer Res. 2017;23(21):6708–6720. doi:10.1158/1078-0432.CCR-17-054428765325

 PubMed Web of Science ®Google Scholar

Christie EL, Fereday S, Doig K, Pattnaik S, Dawson SJ, Bowtell DDL. Reversion of BRCA1/2 germline mutations detected in circulating tumor DNA from patients with high-grade serous ovarian cancer. J Clin Oncol. 2017;35(12):1274–1280. doi:10.1200/JCO.2016.70.462728414925

 PubMed Web of Science ®Google Scholar

Lin KK, Harrell MI, Oza AM, et al. BRCA reversion mutations in circulating tumor DNA predict primary and acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov. 2019;9(2):210–219. doi:10.1158/2159-8290.CD-18-071530425037

 PubMed Web of Science ®Google Scholar

Krimmel JD, Schmitt MW, Harrell MI, et al. Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues. Proc Natl Acad Sci U S A. 2016;113(21):6005–6010. doi:10.1073/pnas.160131111327152024

 PubMed Web of Science ®Google Scholar

Parrella P, Zangen R, Sidransky D, Nicol T. Molecular analysis of peritoneal fluid in ovarian cancer patients. Modern Pathol. 2003;16(7):636–640. doi:10.1097/01.MP.0000076979.28106.ED

 PubMed Web of Science ®Google Scholar

Barquin M, Maximiano C, Perez-Barrios C, et al. Peritoneal washing is an adequate source for somatic BRCA1/2 mutation testing in ovarian malignancies. Pathol Res Pract. 2019;215(2):392–394. doi:10.1016/j.prp.2018.10.02830392916

 PubMed Web of Science ®Google Scholar

Muller HM, Millinger S, Fiegl H, et al. Analysis of methylated genes in peritoneal fluids of ovarian cancer patients: a new prognostic tool. Clin Chem. 2004;50(11):2171–2173.15502091

 PubMed Web of Science ®Google Scholar

Nair N, Camacho-Vanegas O, Rykunov D, et al. Genomic analysis of uterine lavage fluid detects early endometrial cancers and reveals a prevalent landscape of driver mutations in women without histopathologic evidence of cancer: a prospective cross-sectional study. PLoS Med. 2016;13(12):e1002206. doi:10.1371/journal.pmed.100220628027320

 PubMed Web of Science ®Google Scholar

Maritschnegg E, Wang Y, Pecha N, et al. Lavage of the uterine cavity for molecular detection of mullerian duct carcinomas: a proof-of-concept study. J Clin Oncol. 2015;33(36):4293–4300. doi:10.1200/JCO.2015.61.308326552420

 PubMed Web of Science ®Google Scholar

Kinde I, Bettegowda C, Wang Y, et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013;5(167):167ra164. doi:10.1126/scitranslmed.3004952

 Web of Science ®Google Scholar

Wang Y, Li L, Douville C, et al. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med. 2018;10(433). doi:10.1126/scitranslmed.aap8793

 Web of Science ®Google Scholar