Circulating Tumor DNA (ctDNA) refers to fragments of DNA released into the bloodstream by cancer cells. These fragments can be derived from primary tumors, metastases, or dying tumor cells. Analyzing ctDNA is a noninvasive approach that can provide valuable insights into the tumor's genetic makeup, progression, and response to treatment.
Tumor cells release DNA into the bloodstream through apoptosis, necrosis, or active secretion. Represents a fraction of cell-free DNA (cfDNA), including DNA from healthy cells. Detection Methods:
To detect and quantify ctDNA, techniques such as next-generation sequencing (NGS), PCR-based assays, and digital droplet PCR (ddPCR) are used.
Specific biomarkers or mutations (e.g., KRAS, EGFR, or PIK3CA mutations) can be targeted. Applications:
Diagnosis: Helps in the early detection of cancer.
Monitoring: Tracks tumor dynamics over time, including therapy responses and resistance development.
Prognosis: Provides information on tumor burden and potential metastasis.
Minimal Residual Disease (MRD): Detects small amounts of tumor cells remaining after treatment.
Targeted Therapy Selection: Identifies actionable mutations for precision oncology.
Advantages:
Non-invasive (requires a simple blood draw, often called a “liquid biopsy”).
Real-time monitoring of cancer evolution.
Reduces the need for repeated tissue biopsies. Challenges:
Sensitivity: Detecting low levels of ctDNA in the bloodstream, especially in early-stage cancers, can be difficult. Interpretation: Differentiating ctDNA from cfDNA and understanding its clinical significance. Standardization: Lack of uniform protocols for ctDNA testing across laboratories.
Clinical Implications: ctDNA testing is becoming a cornerstone in personalized medicine, enabling oncologists to tailor treatments based on the molecular profile of tumors. It is particularly useful in cancers such as lung, colorectal, and breast cancer. Ongoing research aims to improve the sensitivity of detection methods and expand the use of ctDNA in routine clinical practice.
Circulating tumor DNA for central nervous system germ cell tumor diagnosis.
Primary brain tumors are the most common cause of cancer-related deaths in children and pose difficult questions for the treating physician regarding issues such as the risk/benefit of performing a biopsy, the accuracy of monitoring methods, and the availability of prognostic indicators. It has been recently shown that tumor-specific DNA and proteins can be successfully isolated in liquid biopsies, and it may be possible to exploit this potential as a particularly useful tool for the clinician in addressing these issues.
A review of the current literature was conducted by searching PubMed and Scopus. MeSH terms for the search included “liquid biopsy,” “brain,” “tumor,” and “pediatrics” in all fields. Articles were reviewed to identify the type of brain tumor involved, the method of tumor DNA/protein analysis, and the potential clinical utility. All articles involving primary studies of pediatric brain tumors were included, but reviews were excluded.
The successful isolation of circulating tumor DNA (ctDNA), extracellular vesicles and tumor-specific proteins from liquid biopsies have been consistently demonstrated. This most commonly occurs through CSF analysis, but it has also been successfully demonstrated using plasma and urine samples. Tumor-related gene mutations and alterations in protein expression are identifiable and, in some cases, have been correlated to specific neoplasms. The quantity of ctDNA isolated also appears to have a direct relationship with tumor progression and response to treatment.
The use of liquid biopsies for the diagnosis and monitoring of primary pediatric brain tumors is a foreseeable possibility, as the requisite developmental steps have largely been demonstrated. Increasingly advanced molecular methods are being developed to improve the identification of tumor subtypes and tumor grades, and they may offer a method for monitoring treatment response. These minimally invasive markers will likely be used in the clinical treatment of pediatric brain tumors in the future 1).
2: Azad TD, Jin MC, Bernhardt LJ, Bettegowda C. Liquid biopsy for pediatric diffuse midline glioma: a review of circulating tumor DNA and cerebrospinal fluid tumor DNA. Neurosurg Focus. 2020 Jan 1;48(1):E9. doi: 10.3171/2019.9.FOCUS19699. PubMed PMID: 31896079.
3: Pan Y, Long W, Liu Q. Current Advances and Future Perspectives of Cerebrospinal Fluid Biopsy in Midline Brain Malignancies. Curr Treat Options Oncol. 2019 Nov 29;20(12):88. doi: 10.1007/s11864-019-0689-3. Review. PubMed PMID: 31784837.
4: Megnis K, Peculis R, Rovite V, Laksa P, Niedra H, Balcere I, Caune O, Breiksa A, Nazarovs J, Stukens J, Konrade I, Pirags V, Klovins J. Evaluation of the Possibility to Detect Circulating Tumor DNA From pituitary neuroendocrine tumor. Front Endocrinol (Lausanne). 2019 Sep 18;10:615. doi: 10.3389/fendo.2019.00615. eCollection 2019. PubMed PMID: 31620080; PubMed Central PMCID: PMC6759656.
5: Mattox AK, Yan H, Bettegowda C. The potential of cerebrospinal fluid-based liquid biopsy approaches in CNS tumors. Neuro Oncol. 2019 Dec 17;21(12):1509-1518. doi: 10.1093/neuonc/noz156. PubMed PMID: 31595305; PubMed Central PMCID: PMC6917400.
6: Riebensahm C, Joosse SA, Mohme M, Hanssen A, Matschke J, Goy Y, Witzel I, Lamszus K, Kropidlowski J, Petersen C, Kolb-Kokocinski A, Sauer S, Borgmann K, Glatzel M, Müller V, Westphal M, Riethdorf S, Pantel K, Wikman H. Clonality of circulating tumor cells in breast cancer brain metastasis patients. Breast Cancer Res. 2019 Sep 3;21(1):101. doi: 10.1186/s13058-019-1184-2. PubMed PMID: 31481116; PubMed Central PMCID: PMC6720990.
7: Deniel A, Marguet F, Beaussire L, Tobenas-Dujardin AC, Peillon C, Gambirasio MA, Veresezan O, Magne N, Di Fiore F, Laquerrière A, Sarafan-Vasseur N, Fontanilles M. TERTp Mutation Detection in Plasma by Droplet-Digital Polymerase Chain Reaction in Spinal Myxopapillary Ependymoma with Lung Metastases. World Neurosurg. 2019 Oct;130:405-409. doi: 10.1016/j.wneu.2019.07.111. Epub 2019 Jul 19. PubMed PMID: 31330336.
8: Watanabe J, Natsumeda M, Kanemaru Y, Okada M, Oishi M, Kakita A, Fujii Y. Comparison of circulating tumor DNA between body fluids in patients with primary central nervous system lymphoma. Leuk Lymphoma. 2019 Dec;60(14):3587-3589. doi: 10.1080/10428194.2019.1639169. Epub 2019 Jul 15. PubMed PMID: 31305194.
9: Li JH, He ZQ, Lin FH, Chen ZH, Yang SY, Duan H, Jiang XB, Al-Nahari F, Zhang XH, Wang JH, Zhang GH, Zhang ZF, Li C, Mou YG. Assessment of ctDNA in CSF may be a more rapid means of assessing surgical outcomes than plasma ctDNA in glioblastoma. Mol Cell Probes. 2019 Aug;46:101411. doi: 10.1016/j.mcp.2019.06.001. Epub 2019 Jun 4. PubMed PMID: 31173881.
10: Wei Y, Sun Z, Wang Y, Xie Z, Xu S, Xu Y, Zhou X, Bi J, Zhu Z. Methylation in the TP53 promoter is associated with ischemic stroke. Mol Med Rep. 2019 Aug;20(2):1404-1410. doi: 10.3892/mmr.2019.10348. Epub 2019 Jun 5. PubMed PMID: 31173230.
11: Muluhngwi P, Valdes R Jr, Fernandez-Botran R, Burton E, Williams B, Linder MW. Cell-free DNA diagnostics: current and emerging applications in oncology. Pharmacogenomics. 2019 Apr;20(5):357-380. doi: 10.2217/pgs-2018-0174. Epub 2019 Apr 15. PubMed PMID: 30983510.
12: Sundahl N, Seremet T, Van Dorpe J, Neyns B, Ferdinande L, Meireson A, Brochez L, Kruse V, Ost P. Phase 2 Trial of Nivolumab Combined With Stereotactic Body Radiation Therapy in Patients With Metastatic or Locally Advanced Inoperable Melanoma. Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):828-835. doi: 10.1016/j.ijrobp.2019.03.041. Epub 2019 Apr 3. PubMed PMID: 30951807.
13: Mueller S, Jain P, Liang WS, Kilburn L, Kline C, Gupta N, Panditharatna E, Magge SN, Zhang B, Zhu Y, Crawford JR, Banerjee A, Nazemi K, Packer RJ, Petritsch CK, Truffaux N, Roos A, Nasser S, Phillips JJ, Solomon D, Molinaro A, Waanders AJ, Byron SA, Berens ME, Kuhn J, Nazarian J, Prados M, Resnick AC. A pilot precision medicine trial for children with diffuse intrinsic pontine glioma-PNOC003: A report from the Pacific Pediatric Neuro-Oncology Consortium. Int J Cancer. 2019 Oct 1;145(7):1889-1901. doi: 10.1002/ijc.32258. Epub 2019 Apr 3. PubMed PMID: 30861105.
14: Hallal S, Ebrahimkhani S, Shivalingam B, Graeber MB, Kaufman KL, Buckland ME. The emerging clinical potential of circulating extracellular vesicles for non-invasive glioma diagnosis and disease monitoring. Brain Tumor Pathol. 2019 Apr;36(2):29-39. doi: 10.1007/s10014-019-00335-0. Epub 2019 Mar 11. Review. PubMed PMID: 30859343.
15: In 't Veld SGJG, Wurdinger T. Tumor-educated platelets. Blood. 2019 May 30;133(22):2359-2364. doi: 10.1182/blood-2018-12-852830. Epub 2019 Mar 4. Review. PubMed PMID: 30833413.
16: Hickmann AK, Frick M, Hadaschik D, Battke F, Bittl M, Ganslandt O, Biskup S, Döcker D. Molecular tumor analysis and liquid biopsy: a feasibility investigation analyzing circulating tumor DNA in patients with central nervous system lymphomas. BMC Cancer. 2019 Mar 1;19(1):192. doi: 10.1186/s12885-019-5394-x. PubMed PMID: 30823914; PubMed Central PMCID: PMC6397454.
17: Traylor JI, Kuo JS. “Liquid Biopsy” of Circulating Tumor DNA Characterizes Treatment Response in Pediatric Patients Diffuse Midline Glioma. Neurosurgery. 2019 Aug 1;85(2):E167-E168. doi: 10.1093/neuros/nyz029. PubMed PMID: 30793197.
18: Sundahl N, Vandekerkhove G, Decaestecker K, Meireson A, De Visschere P, Fonteyne V, De Maeseneer D, Reynders D, Goetghebeur E, Van Dorpe J, Verbeke S, Annala M, Brochez L, Van der Eecken K, Wyatt AW, Rottey S, Ost P. Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma. Eur Urol. 2019 May;75(5):707-711. doi: 10.1016/j.eururo.2019.01.009. Epub 2019 Jan 19. PubMed PMID: 30665814.
19: Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, Shukla SA, Hu Z, Li L, Le PM, Allesøe RL, Richman AR, Kowalczyk MS, Abdelrahman S, Geduldig JE, Charbonneau S, Pelton K, Iorgulescu JB, Elagina L, Zhang W, Olive O, McCluskey C, Olsen LR, Stevens J, Lane WJ, Salazar AM, Daley H, Wen PY, Chiocca EA, Harden M, Lennon NJ, Gabriel S, Getz G, Lander ES, Regev A, Ritz J, Neuberg D, Rodig SJ, Ligon KL, Suvà ML, Wucherpfennig KW, Hacohen N, Fritsch EF, Livak KJ, Ott PA, Wu CJ, Reardon DA. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019 Jan;565(7738):234-239. doi: 10.1038/s41586-018-0792-9. Epub 2018 Dec 19. PubMed PMID: 30568305; PubMed Central PMCID: PMC6546179.
20: Zorofchian S, Iqbal F, Rao M, Aung PP, Esquenazi Y, Ballester LY. Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies. J Clin Pathol. 2019 Apr;72(4):271-280. doi: 10.1136/jclinpath-2018-205414. Epub 2018 Nov 22. Review. PubMed PMID: 30467241.
21: Pan C, Diplas BH, Chen X, Wu Y, Xiao X, Jiang L, Geng Y, Xu C, Sun Y, Zhang P, Wu W, Wang Y, Wu Z, Zhang J, Jiao Y, Yan H, Zhang L. Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA. Acta Neuropathol. 2019 Feb;137(2):297-306. doi: 10.1007/s00401-018-1936-6. Epub 2018 Nov 20. PubMed PMID: 30460397.
22: Ramayanti O, Verkuijlen SAWM, Novianti P, Scheepbouwer C, Misovic B, Koppers-Lalic D, van Weering J, Beckers L, Adham M, Martorelli D, Middeldorp JM, Pegtel DM. Vesicle-bound EBV-BART13-3p MicroRNA in circulation distinguishes nasopharyngeal from other head and neck cancer and asymptomatic EBV-infections. Int J Cancer. 2019 May 15;144(10):2555-2566. doi: 10.1002/ijc.31967. Epub 2018 Dec 6. PubMed PMID: 30411781; PubMed Central PMCID: PMC6587801.
23: Mouliere F, Chandrananda D, Piskorz AM, Moore EK, Morris J, Ahlborn LB, Mair R, Goranova T, Marass F, Heider K, Wan JCM, Supernat A, Hudecova I, Gounaris I, Ros S, Jimenez-Linan M, Garcia-Corbacho J, Patel K, Østrup O, Murphy S, Eldridge MD, Gale D, Stewart GD, Burge J, Cooper WN, van der Heijden MS, Massie CE, Watts C, Corrie P, Pacey S, Brindle KM, Baird RD, Mau-Sørensen M, Parkinson CA, Smith CG, Brenton JD, Rosenfeld N. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med. 2018 Nov 7;10(466). pii: eaat4921. doi: 10.1126/scitranslmed.aat4921. PubMed PMID: 30404863; PubMed Central PMCID: PMC6483061.
24: Mouliere F, Mair R, Chandrananda D, Marass F, Smith CG, Su J, Morris J, Watts C, Brindle KM, Rosenfeld N. Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients. EMBO Mol Med. 2018 Dec;10(12). pii: e9323. doi: 10.15252/emmm.201809323. PubMed PMID: 30401727; PubMed Central PMCID: PMC6284385.
25: Mair R, Mouliere F, Smith CG, Chandrananda D, Gale D, Marass F, Tsui DWY, Massie CE, Wright AJ, Watts C, Rosenfeld N, Brindle KM. Measurement of Plasma Cell-Free Mitochondrial Tumor DNA Improves Detection of Glioblastoma in Patient-Derived Orthotopic Xenograft Models. Cancer Res. 2019 Jan 1;79(1):220-230. doi: 10.1158/0008-5472.CAN-18-0074. Epub 2018 Nov 2. PubMed PMID: 30389699; PubMed Central PMCID: PMC6753020.
26: Panditharatna E, Kilburn LB, Aboian MS, Kambhampati M, Gordish-Dressman H, Magge SN, Gupta N, Myseros JS, Hwang EI, Kline C, Crawford JR, Warren KE, Cha S, Liang WS, Berens ME, Packer RJ, Resnick AC, Prados M, Mueller S, Nazarian J. Clinically Relevant and Minimally Invasive Tumor Surveillance of Pediatric Diffuse Midline Gliomas Using Patient-Derived Liquid Biopsy. Clin Cancer Res. 2018 Dec 1;24(23):5850-5859. doi: 10.1158/1078-0432.CCR-18-1345. Epub 2018 Oct 15. PubMed PMID: 30322880; PubMed Central PMCID: PMC6279526.
27: Zorofchian S, Lu G, Zhu JJ, Duose DY, Windham J, Esquenazi Y, Ballester LY. Detection of the MYD88 p.L265P Mutation in the CSF of a Patient With Secondary Central Nervous System Lymphoma. Front Oncol. 2018 Sep 20;8:382. doi: 10.3389/fonc.2018.00382. eCollection 2018. PubMed PMID: 30294590; PubMed Central PMCID: PMC6158312.
28: Stallard S, Savelieff MG, Wierzbicki K, Mullan B, Miklja Z, Bruzek A, Garcia T, Siada R, Anderson B, Singer BH, Hashizume R, Carcaboso AM, McMurray KQ, Heth J, Muraszko K, Robertson PL, Mody R, Venneti S, Garton H, Koschmann C. CSF H3F3A K27M circulating tumor DNA copy number quantifies tumor growth and in vitro treatment response. Acta Neuropathol Commun. 2018 Aug 15;6(1):80. doi: 10.1186/s40478-018-0580-7. PubMed PMID: 30111355; PubMed Central PMCID: PMC6094898.
29: Juratli TA, Stasik S, Zolal A, Schuster C, Richter S, Daubner D, Juratli MA, Thowe R, Hennig S, Makina M, Meinhardt M, Lautenschlaeger T, Schackert G, Krex D, Thiede C. TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study. Clin Cancer Res. 2018 Nov 1;24(21):5282-5291. doi: 10.1158/1078-0432.CCR-17-3717. Epub 2018 Jun 25. PubMed PMID: 29941484.
30: Best MG, Wesseling P, Wurdinger T. Tumor-Educated Platelets as a Noninvasive Biomarker Source for Cancer Detection and Progression Monitoring. Cancer Res. 2018 Jul 1;78(13):3407-3412. doi: 10.1158/0008-5472.CAN-18-0887. Epub 2018 Jun 19. Review. PubMed PMID: 29921699.
31: Ballester LY, Glitza Oliva IC, Douse DY, Chen MM, Lan C, Haydu LE, Huse JT, Roy-Chowdhuri S, Luthra R, Wistuba II, Davies MA. Evaluating Circulating Tumor DNA From the Cerebrospinal Fluid of Patients With Melanoma and Leptomeningeal Disease. J Neuropathol Exp Neurol. 2018 Jul 1;77(7):628-635. doi: 10.1093/jnen/nly046. PubMed PMID: 29873738; PubMed Central PMCID: PMC6005029.
32: Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud AB, Speranza MC, Nakashima H, Hayes JL, Lee K, Balaj L, Passaro C, Rooj AK, Krasemann S, Carter BS, Chen CC, Steed T, Treiber J, Rodig S, Yang K, Nakano I, Lee H, Weissleder R, Breakefield XO, Godlewski J, Westphal M, Lamszus K, Freeman GJ, Bronisz A, Lawler SE, Chiocca EA. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv. 2018 Mar 7;4(3):eaar2766. doi: 10.1126/sciadv.aar2766. eCollection 2018 Mar. PubMed PMID: 29532035; PubMed Central PMCID: PMC5842038.
33: Stewart CM, Kothari PD, Mouliere F, Mair R, Somnay S, Benayed R, Zehir A, Weigelt B, Dawson SJ, Arcila ME, Berger MF, Tsui DW. The value of cell-free DNA for molecular pathology. J Pathol. 2018 Apr;244(5):616-627. doi: 10.1002/path.5048. Epub 2018 Mar 12. Review. PubMed PMID: 29380875; PubMed Central PMCID: PMC6656375.
34: Paret C, Russo A, Otto H, Mayer A, Zahnreich S, Wagner W, Samuel D, Scharnhorst D, Solomon DA, Dhall G, Wong K, Bender H, Alt F, Wingerter A, Neu MA, Beck O, Prawitt D, Eder S, Henninger N, El Malki K, Lehmann N, Backes N, Roth L, Seidmann L, Sommer C, Brockmann MA, Staatz G, Schmidberger H, Faber J. Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy. Oncotarget. 2017 Dec 11;8(69):114210-114225. doi: 10.18632/oncotarget.23174. eCollection 2017 Dec 26. PubMed PMID: 29371980; PubMed Central PMCID: PMC5768397.
35: Taillibert S, Chamberlain MC. Leptomeningeal metastasis. Handb Clin Neurol. 2018;149:169-204. doi: 10.1016/B978-0-12-811161-1.00013-X. Review. PubMed PMID: 29307353.
36: Wu CP, Wu P, Zhao HF, Liu WL, Li WP. Clinical Applications of and Challenges in Single-Cell Analysis of Circulating Tumor Cells. DNA Cell Biol. 2018 Feb;37(2):78-89. doi: 10.1089/dna.2017.3981. Epub 2017 Dec 21. Review. PubMed PMID: 29265876.
37: Hattori K, Sakata-Yanagimoto M, Suehara Y, Yokoyama Y, Kato T, Kurita N, Nishikii H, Obara N, Takano S, Ishikawa E, Matsumura A, Hasegawa Y, Chiba S. Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma. Cancer Sci. 2018 Jan;109(1):225-230. doi: 10.1111/cas.13450. Epub 2017 Dec 23. PubMed PMID: 29151258; PubMed Central PMCID: PMC5765295.
38: Verheul C, Kleijn A, Lamfers MLM. Cerebrospinal fluid biomarkers of malignancies located in the central nervous system. Handb Clin Neurol. 2017;146:139-169. doi: 10.1016/B978-0-12-804279-3.00010-1. Review. PubMed PMID: 29110768.
39: Connolly ID, Li Y, Pan W, Johnson E, You L, Vogel H, Ratliff J, Hayden Gephart M. A pilot study on the use of cerebrospinal fluid cell-free DNA in intramedullary spinal ependymoma. J Neurooncol. 2017 Oct;135(1):29-36. doi: 10.1007/s11060-017-2557-y. Epub 2017 Sep 12. PubMed PMID: 28900844.
40: Shankar GM, Balaj L, Stott SL, Nahed B, Carter BS. Liquid biopsy for brain tumors. Expert Rev Mol Diagn. 2017 Oct;17(10):943-947. doi: 10.1080/14737159.2017.1374854. Epub 2017 Sep 6. Review. PubMed PMID: 28875730; PubMed Central PMCID: PMC5856481.
41: Song CX, Yin S, Ma L, Wheeler A, Chen Y, Zhang Y, Liu B, Xiong J, Zhang W, Hu J, Zhou Z, Dong B, Tian Z, Jeffrey SS, Chua MS, So S, Li W, Wei Y, Diao J, Xie D, Quake SR. 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Res. 2017 Oct;27(10):1231-1242. doi: 10.1038/cr.2017.106. Epub 2017 Aug 18. PubMed PMID: 28820176; PubMed Central PMCID: PMC5630676.
42: Xie G, Gu D, Zhang L, Chen S, Wu D. A rapid and systemic complete response to stereotactic body radiation therapy and pembrolizumab in a patient with metastatic renal cell carcinoma. Cancer Biol Ther. 2017 Aug 3;18(8):547-551. doi: 10.1080/15384047.2017.1345389. Epub 2017 Jun 30. PubMed PMID: 28665741; PubMed Central PMCID: PMC5652971.
43: Radwan N, Phillips R, Ross A, Rowe SP, Gorin MA, Antonarakis ES, Deville C, Greco S, Denmeade S, Paller C, Song DY, Diehn M, Wang H, Carducci M, Pienta KJ, Pomper MG, DeWeese TL, Dicker A, Eisenberger M, Tran PT. A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE). BMC Cancer. 2017 Jun 29;17(1):453. doi: 10.1186/s12885-017-3455-6. PubMed PMID: 28662647; PubMed Central PMCID: PMC5492934.
44: Fontanilles M, Marguet F, Bohers É, Viailly PJ, Dubois S, Bertrand P, Camus V, Mareschal S, Ruminy P, Maingonnat C, Lepretre S, Veresezan EL, Derrey S, Tilly H, Picquenot JM, Laquerrière A, Jardin F. Non-invasive detection of somatic mutations using next-generation sequencing in primary central nervous system lymphoma. Oncotarget. 2017 Jul 18;8(29):48157-48168. doi: 10.18632/oncotarget.18325. PubMed PMID: 28636991; PubMed Central PMCID: PMC5564634.
45: Sharabi A, Kim SS, Kato S, Sanders PD, Patel SP, Sanghvi P, Weihe E, Kurzrock R. Exceptional Response to Nivolumab and Stereotactic Body Radiation Therapy (SBRT) in Neuroendocrine Cervical Carcinoma with High Tumor Mutational Burden: Management Considerations from the Center For Personalized Cancer Therapy at UC San Diego Moores Cancer Center. Oncologist. 2017 Jun;22(6):631-637. doi: 10.1634/theoncologist.2016-0517. Epub 2017 May 26. PubMed PMID: 28550027; PubMed Central PMCID: PMC5469598.
46: Uzilov AV, Cheesman KC, Fink MY, Newman LC, Pandya C, Lalazar Y, Hefti M, Fowkes M, Deikus G, Lau CY, Moe AS, Kinoshita Y, Kasai Y, Zweig M, Gupta A, Starcevic D, Mahajan M, Schadt EE, Post KD, Donovan MJ, Sebra R, Chen R, Geer EB. Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma. Cold Spring Harb Mol Case Stud. 2017 May;3(3):a001602. doi: 10.1101/mcs.a001602. PubMed PMID: 28487882; PubMed Central PMCID: PMC5411693.
47: Bloch O, Lim M, Sughrue ME, Komotar RJ, Abrahams JM, O'Rourke DM, D'Ambrosio A, Bruce JN, Parsa AT. Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma: Impact of Peripheral PD-L1 Expression on Response to Therapy. Clin Cancer Res. 2017 Jul 15;23(14):3575-3584. doi: 10.1158/1078-0432.CCR-16-1369. Epub 2017 Feb 13. PubMed PMID: 28193626; PubMed Central PMCID: PMC5511566.
48: Wang J, Bettegowda C. Applications of DNA-Based Liquid Biopsy for Central Nervous System Neoplasms. J Mol Diagn. 2017 Jan;19(1):24-34. doi: 10.1016/j.jmoldx.2016.08.007. Epub 2016 Nov 15. Review. PubMed PMID: 27863260.
49: Goodwin CR, Abu-Bonsrah N, Bilsky MH, Reynolds JJ, Rhines LD, Laufer I, Disch AC, Bozsodi A, Patel SR, Gokaslan ZL, Sciubba DM, Bettegowda C. Clinical Decision Making: Integrating Advances in the Molecular Understanding of Spine Tumors. Spine (Phila Pa 1976). 2016 Oct 15;41 Suppl 20:S171-S177. Review. PubMed PMID: 27488298.
50: Fan CH, Chang EL, Ting CY, Lin YC, Liao EC, Huang CY, Chang YC, Chan HL, Wei KC, Yeh CK. Folate-conjugated gene-carrying microbubbles with focused ultrasound for concurrent blood-brain barrier opening and local gene delivery. Biomaterials. 2016 Nov;106:46-57. doi: 10.1016/j.biomaterials.2016.08.017. Epub 2016 Aug 12. PubMed PMID: 27544926.
51: Hayashi M, Chu D, Meyer CF, Llosa NJ, McCarty G, Morris CD, Levin AS, Wolinsky JP, Albert CM, Steppan DA, Park BH, Loeb DM. Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA. Cancer. 2016 Oct;122(19):3015-23. doi: 10.1002/cncr.30144. Epub 2016 Jun 28. PubMed PMID: 27351911; PubMed Central PMCID: PMC5102400.
52: Ye B, Gao Q, Zeng Z, Stary CM, Jian Z, Xiong X, Gu L. Single-Cell Sequencing Technology in Oncology: Applications for Clinical Therapies and Research. Anal Cell Pathol (Amst). 2016;2016:9369240. doi: 10.1155/2016/9369240. Epub 2016 May 25. Review. PubMed PMID: 27313981; PubMed Central PMCID: PMC4897661.
53: Connolly ID, Li Y, Gephart MH, Nagpal S. The “Liquid Biopsy”: the Role of Circulating DNA and RNA in Central Nervous System Tumors. Curr Neurol Neurosci Rep. 2016 Mar;16(3):25. doi: 10.1007/s11910-016-0629-6. Review. PubMed PMID: 26838352.
54: Qian Z, Shen Q, Yang X, Qiu Y, Zhang W. The Role of Extracellular Vesicles: An Epigenetic View of the Cancer Microenvironment. Biomed Res Int. 2015;2015:649161. doi: 10.1155/2015/649161. Epub 2015 Oct 25. Review. PubMed PMID: 26582468; PubMed Central PMCID: PMC4637039.
55: Westphal M, Lamszus K. Circulating biomarkers for gliomas. Nat Rev Neurol. 2015 Oct;11(10):556-66. doi: 10.1038/nrneurol.2015.171. Epub 2015 Sep 15. Review. PubMed PMID: 26369507.
56: Barault L, Amatu A, Bleeker FE, Moutinho C, Falcomatà C, Fiano V, Cassingena A, Siravegna G, Milione M, Cassoni P, De Braud F, Rudà R, Soffietti R, Venesio T, Bardelli A, Wesseling P, de Witt Hamer P, Pietrantonio F, Siena S, Esteller M, Sartore-Bianchi A, Di Nicolantonio F. Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer. Ann Oncol. 2015 Sep;26(9):1994-9. doi: 10.1093/annonc/mdv272. Epub 2015 Jun 25. PubMed PMID: 26113646.
57: Braig F, März M, Schieferdecker A, Schulte A, Voigt M, Stein A, Grob T, Alawi M, Indenbirken D, Kriegs M, Engel E, Vanhoefer U, Grundhoff A, Loges S, Riecken K, Fehse B, Bokemeyer C, Binder M. Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer. Oncotarget. 2015 May 20;6(14):12035-47. PubMed PMID: 26059438; PubMed Central PMCID: PMC4494921.
58: Forsyth TM, Bi WL, Abedalthagafi M, Dunn IF, Chiocca EA. Extracranial growth of glioblastoma multiforme. J Clin Neurosci. 2015 Sep;22(9):1521-3. doi: 10.1016/j.jocn.2015.03.018. Epub 2015 May 5. PubMed PMID: 25956620.
59: Pan W, Gu W, Nagpal S, Gephart MH, Quake SR. Brain tumor mutations detected in cerebral spinal fluid. Clin Chem. 2015 Mar;61(3):514-22. doi: 10.1373/clinchem.2014.235457. Epub 2015 Jan 20. PubMed PMID: 25605683; PubMed Central PMCID: PMC5412506.
60: Martens T, Matschke J, Müller C, Riethdorf S, Balabanov S, Westphal M, Heese O. Skeletal spread of an anaplastic astrocytoma (WHO grade III) and preservation of histopathological properties within metastases. Clin Neurol Neurosurg. 2013 Mar;115(3):323-8. doi: 10.1016/j.clineuro.2012.05.025. Epub 2012 Jun 14. PubMed PMID: 22704562.
61: Debinski W, Gibo D, Mintz A. Epigenetics in high-grade astrocytomas: opportunities for prevention and detection of brain tumors. Ann N Y Acad Sci. 2003 Mar;983:232-42. Review. PubMed PMID: 12724228.
62: Nakasu S, Nakajima M, Nakazawa T, Nakasu Y, Handa J. p53 accumulation and apoptosis in embolized meningiomas. Acta Neuropathol. 1997 Jun;93(6):599-605. PubMed PMID: 9194899.
63: Ooi GT, Cohen FJ, Tseng LY, Rechler MM, Boisclair YR. Growth hormone stimulates transcription of the gene encoding the acid-labile subunit (ALS) of the circulating insulin-like growth factor-binding protein complex and ALS promoter activity in rat liver. Mol Endocrinol. 1997 Jun;11(7):997-1007. PubMed PMID: 9178759.
64: Fagin JA, Brown A, Melmed S. Regulation of pituitary insulin-like growth factor-I messenger ribonucleic acid levels in rats harboring somatomammotropic tumors: implications for growth hormone autoregulation. Endocrinology. 1988 May;122(5):2204-10. PubMed PMID: 3359980.