IDH1 p.R132H ctDNA and D-2-hydroxyglutarate as CSF biomarkers in patients with IDH-mutant gliomas

被引：23

作者：

Fujita, Yoko ^{[1
]}

Nunez-Rubiano, Luis ^{[2
]}

Dono, Antonio ^{[1
]}

Bellman, Allison ^{[3
]}

Shah, Mauli ^{[9
]}

Rodriguez, Juan C. ^{[1
]}

Putluri, Vasanta ^{[5
]}

Kamal, Abu Hena Mostafa ^{[5
]}

Putluri, Nagireddy ^{[5
,6
]}

Riascos, Roy F. ^{[2
,7
]}

Zhu, Jay-Jiguang ^{[1
,7
]}

Esquenazi, Yoshua ^{[1
,7
,8
]}

Ballester, Leomar Y. ^{[4
,9
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Vivian L Smith Dept Neurosurg, 6431 Fannin St, Houston, TX 77030 USA

[2] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Radiol, Houston, TX 77030 USA

[3] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Pathol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd,Unit 85, Houston, TX 77030 USA

[5] Baylor Coll Med, Metabol Core, Adv Technol Core, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[7] Mem Hermann Hosp TMC, Houston, TX 77030 USA

[8] Univ Texas Hlth Sci Ctr Houston, Ctr Precis Hlth, McGovern Med Sch, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, 2130 West Holcombe Blvd, Houston, TX 77030 USA

来源：

JOURNAL OF NEURO-ONCOLOGY | 2022年 / 159卷 / 02期

基金：

美国国家卫生研究院;

关键词：

D-2-hydroxyglutarate (D-2HG); IDH1; Gliomas; Cerebrospinal fluid; Circulating tumor DNA; Oligodendroglioma; Astrocytoma; CENTRAL-NERVOUS-SYSTEM; GENOMIC ANALYSIS; MUTATIONS; METABOLISM; INHIBITOR;

D O I：

10.1007/s11060-022-04060-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas. Methods CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images. Results The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 of the 9 samples from patients with IDH-mutant glioma, and IDH1 p.R132H mutation was detected in 5 of the 7 samples. The MAF ranged from 0.3 to 39.95%. Total 2HG level, D-2HG level, and D/L-2HG ratio in CSF were significantly higher in patients with IDH-mutant gliomas than in patients with IDH-wildtype gliomas. D-2HG level and D/L-2HG ratio correlated with total tumor volume in patients with IDH-mutant gliomas but not in patients with IDH-wildtype gliomas. Conclusion Our results suggest that detection of IDH1 p.R132H mutation by ddPCR and increased D-2HG level in CSF may help identify IDH-mutant gliomas. Our results also suggest that D-2HG level and D/L-2HG ratio correlate with tumor volume in patients with IDH-mutant gliomas. Further prospective studies with larger cohorts are needed to validate these findings.

引用

页码：261 / 270

页数：10

共 28 条

[1] Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival [J].

Amara, Chandra Sekhar ;

Ambati, Chandrashekar R. ;

Vantaku, Venkatrao ;

Piyarathna, Danthasinghe Waduge Badrajee ;

Donepudi, Ramya ;

Ravi, Shiva Shankar ;

Arnold, James M. ;

Putluri, Vasanta ;

Chatta, Gurkamal ;

Guru, Khurshid A. ;

Badr, Hoda ;

Terris, Martha K. ;

Bollag, Roni J. ;

Sreekumar, Arun ;

Apolo, Andrea B. ;

Putluri, Nagireddy .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2019, 28 (04) :770-781

[2] Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors [J].

Ballester, Leomar Y. ;

Lu, Guangrong ;

Zorofchian, Soheil ;

Vantaku, Venkatrao ;

Putluri, Vasanta ;

Yan, Yuanqing ;

Arevalo, Octavio ;

Zhu, Ping ;

Riascos, Roy F. ;

Sreekumar, Arun ;

Esquenazi, Yoshua ;

Putluri, Nagireddy ;

Zhu, Jay-Jiguang .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2018, 6 :85

[3] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[4] Altered cellular metabolism in gliomas - an emerging landscape of actionable co-dependency targets [J].

Bi, Junfeng ;

Chowdhry, Sudhir ;

Wu, Sihan ;

Zhang, Wenjing ;

Masui, Kenta ;

Mischel, Paul S. .

NATURE REVIEWS CANCER, 2020, 20 (01) :57-70

[5] Frequent Mutation of Isocitrate Dehydrogenase (IDH)1 and IDH2 in Cholangiocarcinoma Identified Through Broad-Based Tumor Genotyping [J].

Borger, Darrell R. ;

Tanabe, Kenneth K. ;

Fan, Kenneth C. ;

Lopez, Hector U. ;

Fantin, Valeria R. ;

Straley, Kimberly S. ;

Schenkein, David P. ;

Hezel, Aram F. ;

Ancukiewicz, Marek ;

Liebman, Hannah M. ;

Kwak, Eunice L. ;

Clark, Jeffrey W. ;

Ryan, David P. ;

Deshpande, Vikram ;

Dias-Santagata, Dora ;

Ellisen, Leif W. ;

Zhu, Andrew X. ;

Iafrate, A. John .

ONCOLOGIST, 2012, 17 (01) :72-79

[6] Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas [J].

Brat, Daniel J. ;

Verhaak, Roel G. W. ;

Al-dape, Kenneth D. ;

Yung, W. K. Alfred ;

Salama, Sofie R. ;

Cooper, Lee A. D. ;

Rheinbay, Esther ;

Miller, C. Ryan ;

Vitucci, Mark ;

Morozova, Olena ;

Robertson, A. Gordon ;

Noushmehr, Houtan ;

Laird, Peter W. ;

Cherniack, Andrew D. ;

Akbani, Rehan ;

Huse, Jason T. ;

Ciriello, Giovanni ;

Poisson, Laila M. ;

Barnholtz-Sloan, Jill S. ;

Berger, Mitchel S. ;

Brennan, Cameron ;

Colen, Rivka R. ;

Colman, Howard ;

Flanders, Adam E. ;

Giannini, Caterina ;

Grifford, Mia ;

Iavarone, Antonio ;

Jain, Rajan ;

Joseph, Isaac ;

Kim, Jaegil ;

Kasaian, Katayoon ;

Mikkelsen, Tom ;

Murray, Bradley A. ;

O'Neill, Brian Patrick ;

Pachter, Lior ;

Parsons, Donald W. ;

Sougnez, Carrie ;

Sulman, Erik P. ;

Vandenberg, Scott R. ;

Van Meir, Erwin G. ;

von Deimling, Andreas ;

Zhang, Hailei ;

Crain, Daniel ;

Lau, Kevin ;

Mallery, David ;

Morris, Scott ;

Paulauskis, Joseph ;

Penny, Robert ;

Shelton, Troy ;

Sherman, Mark .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2481-2498

[7] Cancer-associated IDH1 mutations produce 2-hydroxyglutarate [J].

Dang, Lenny ;

White, David W. ;

Gross, Stefan ;

Bennett, Bryson D. ;

Bittinger, Mark A. ;

Driggers, Edward M. ;

Fantin, Valeria R. ;

Jang, Hyun Gyung ;

Jin, Shengfang ;

Keenan, Marie C. ;

Marks, Kevin M. ;

Prins, Robert M. ;

Ward, Patrick S. ;

Yen, Katharine E. ;

Liau, Linda M. ;

Rabinowitz, Joshua D. ;

Cantley, Lewis C. ;

Thompson, Craig B. ;

Heiden, Matthew G. Vander ;

Su, Shinsan M. .

NATURE, 2009, 462 (7274) :739-U52

[8] Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma [J].

De Mattos-Arruda, Leticia ;

Mayor, Regina ;

Ng, Charlotte K. Y. ;

Weigelt, Britta ;

Martinez-Ricarte, Francisco ;

Torrejon, Davis ;

Oliveira, Mafalda ;

Arias, Alexandra ;

Raventos, Carolina ;

Tang, Jiabin ;

Guerini-Rocco, Elena ;

Martinez-Saez, Elena ;

Lois, Sergio ;

Marin, Oscar ;

de la Cruz, Xavier ;

Piscuoglio, Salvatore ;

Towers, Russel ;

Vivancos, Ana ;

Peg, Vicente ;

Ramon y Cajal, Santiago ;

Carles, Joan ;

Rodon, Jordi ;

Gonzalez-Cao, Maria ;

Tabernero, Josep ;

Felip, Enriqueta ;

Sahuquillo, Joan ;

Berger, Michael F. ;

Cortes, Javier ;

Reis-Filho, Jorge S. ;

Seoane, Joan .

NATURE COMMUNICATIONS, 2015, 6

[9] Selective Detection of the D-enantiomer of 2-Hydroxyglutarate in the CSF of Glioma Patients with Mutated Isocitrate Dehydrogenase [J].

Kalinina, Juliya ;

Ahn, Jun ;

Devi, Narra S. ;

Wang, Liya ;

Li, Yuancheng ;

Olson, Jeffrey J. ;

Glantz, Michael ;

Smith, Thomas ;

Kim, Ella L. ;

Giese, Alf ;

Jensen, Randy L. ;

Chen, Clark C. ;

Carter, Bob S. ;

Mao, Hui ;

He, Miao ;

Van Meir, Erwin G. .

CLINICAL CANCER RESEARCH, 2016, 22 (24) :6256-6265

[10] Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma [J].

Locasale, Jason W. ;

Melman, Tamar ;

Song, Susan ;

Yang, Xuemei ;

Swanson, Kenneth D. ;

Cantley, Lewis C. ;

Wong, Eric T. ;

Asara, John M. .

MOLECULAR & CELLULAR PROTEOMICS, 2012, 11 (06)

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