Circulating cell-free DNA and IL-10 from cerebrospinal fluids aid primary vitreoretinal lymphoma diagnosis

Zhuang, Zhe; Zhang, Yan; Zhang, Xiao; Zhang, Meifen; Zou, Dongmei; Zhang, Li; Jia, Congwei; Zhang, Wei

doi:10.3389/fonc.2022.955080

Cited by 5 publications

(3 citation statements)

References 57 publications

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“…All seven of the newly diagnosed PCNSL patients had MYDL265P in their CSF cfDNA or baseline IL-10 ≥ 8.2 pg/ml, the latter of which has been shown to help diagnose CNSL [12]. Hence, the combination of CSF cfDNA and IL-10 may do an even better job of diagnosing CNSL, a result we have already found with PIOL [21].…”

Section: Journal Of Oncologymentioning

confidence: 73%

“…MYD88, CD79B, and other NF- κ B-pathway-related mutations promote IL-10 expression by lymphoma cells [ 15 , 16 , 20 ], and IL-10 has also been found to express in CD68 + and CD163 + tumor-associated macrophages by double immunostaining analysis [ 21 ]. Thus, we speculate that CSF cfDNA and IL-10 are generated in different ways, the former from tumor cells and the latter from both tumor cells and the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

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Cell-Free DNA in Cerebrospinal Fluid Complements the Monitoring Value of Interleukin-10 in Newly Diagnosed Primary Central Nervous System Lymphoma

Wang

Zou

Zhuang

et al. 2023

Journal of Oncology

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Objectives. Primary central nervous system lymphoma (PCNSL) usually has a poor prognosis. Cerebrospinal fluid (CSF) interleukin (IL)-10 has shown diagnostic, prognostic, and monitoring value in our previous studies. Cell-free circulating tumor DNA can be detected in the CSF of refractory/relapse cases and has also shown monitoring value. However, information about its monitoring value in newly diagnosed PCNSL patients and comparisons of CSF IL-10 and CSF cell-free DNA (cfDNA) are scarce. Methods. We performed next-generation sequencing on paraffin-embedded tissue and the serial CSF cfDNA of 10 newly diagnosed PCNSL patients and on the baseline CSF cfDNA of 11 other central nervous system lymphoma patients. We also monitored the CSF IL-10 levels of the 10 newly diagnosed PCNSL patients. Results. In seven newly diagnosed PCNSL patients with sufficient baseline CSF cfDNA, six had ≥1 mutated genes in their CSF cfDNA. The most common were MYD88(4/7), PIM1(3/7), MLL2(3/7), and ETV6(2/7). We also identified multiple somatic mutations, most commonly in PIM1. MYD88L265P can be detected in both tumor tissue and CSF cfDNA. The genomic profiles of CFS cfDNA were similar in PCNSL and PIOL patients. Newly diagnosed PCNSL patients with persistently positive cfDNA and negative IL-10 progressed quickly, while those with negative cfDNA and negative IL-10 were in maintenance therapy for more than 18 months. Two patients without cfDNA had increased CSF IL-10 concentrations before disease relapse. These results indicate that negative CSF cfDNA predicts better results, and persistently positive CSF cfDNA predicts disease progression earlier than conventional magnetic resonance imaging. Conclusion. In conclusion, CSF cfDNA is a potential predictor of relapse and progression, which complements the monitoring value of CSF IL-10 in newly diagnosed PCNSL patients.

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Section: Journal Of Oncologymentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Cell-Free DNA in Cerebrospinal Fluid Complements the Monitoring Value of Interleukin-10 in Newly Diagnosed Primary Central Nervous System Lymphoma

Wang

Zou

Zhuang

et al. 2023

Journal of Oncology

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“…Liquid biopsy can use a small amount of fluid; the analysis involves modern technology: next generation sequencing (NGS), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA). In recent years, cfDNA sequencing from the aqueous humor, vitreous fluid, or cerebrospinal fluid (CSF) of VRL patients has been evaluated for identifying genomic mutations [32,[34][35][36][37][38][39] . The data reveal high sensitivity and specificity.…”

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confidence: 99%

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2024

Int J Ophthalmol

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Great discoveries and improvements invariably involvethe cooperation of many minds. -Alexander Graham Bell The hardest problems of pure and applied science can only be solved by the open collaboration of the worldwide scientific community. -Kenneth G Wilson O n December 9, 2023, I was privileged to be honored and participate in the Dr. Chi Chao Chan Symposium on Global Collaboration of Eye Research as the Global Eye Genetic Consortium (GEGC) session, which was held in the 16 th Congress of the Asia-Pacific Vitreo-Retina Society (APVRS) in Hong Kong. Along with my talk on "Global collaboration of eye research: personal experience", other prominent international speakers provided their own perspectives on opportunities for networking, collaboration,

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Vitreoretinal lymphoma: the importance of cerebral spinal fluid evaluation at initial diagnosis

Silverman,

Abramson,

Canestraro

et al. 2024

Br J Ophthalmol

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Background/aimsTo determine if patients with vitreoretinal lymphoma (VRL) and concomitant central nervous system lymphoma (CNSL) may present without brain MRI findings, but possess cerebrospinal fluid (CSF) suspicious for lymphoma.MethodsThis was a retrospective, single-centre, observational study evaluating patients with a diagnosis or suspicion of VRL seen at Memorial Sloan Kettering Cancer Center between 2006 and 2024. Patients were included if the final diagnosis was biopsy-proven CNSL and both MRI brain with and without contrast±CSF evaluation (obligatory for inclusion if MRI negative) were performed at the initial diagnostic workup. Patients were excluded if CNS disease treatment (brain, spine or CSF) preceded ocular disease. Patients with prior extra-CNS disease were included. Clinical records and radiographic imaging were retrospectively reviewed and relevant data were recorded for each patient. We evaluated the proportion of patients with MRI negative and CSF suspicious for lymphoma. Subgroup analysis included imaging features, pathology, treatment and disease course.ResultsWe identified 65 patients. Of the 65 patients at the presentation of VRL, 30 had negative MRI brain and CSF, 16 had positive brain MRI and negative CSF and 8 had both positive MRI brain and CSF. 11 (16.9%) had CSF suspicious for lymphoma without positive findings on MRI of the brain. In this subgroup, the median age was 66 years (range 49–82) and 36% were female. 86% of these patients were asymptomatic neurologically. 73% underwent systemic treatment. At a mean 3 years follow-up, 91% of patients were living.ConclusionIn patients with suspected VRL, it is possible to have CSF test positive for lymphoma in the context of negative brain MRI. This suggests, when evaluating VRL patients for concomitant CNS disease, CSF evaluation leads to earlier detection and systemic treatment, even when MRI brain findings are negative. In our cohort, an absence of CSF evaluation in the context of negative brain MRI could have missed 16.9% of patients with CNS lymphoma.

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Circulating cell-free DNA and IL-10 from cerebrospinal fluids aid primary vitreoretinal lymphoma diagnosis

Cited by 5 publications

References 57 publications

Cell-Free DNA in Cerebrospinal Fluid Complements the Monitoring Value of Interleukin-10 in Newly Diagnosed Primary Central Nervous System Lymphoma

Cell-Free DNA in Cerebrospinal Fluid Complements the Monitoring Value of Interleukin-10 in Newly Diagnosed Primary Central Nervous System Lymphoma

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Vitreoretinal lymphoma: the importance of cerebral spinal fluid evaluation at initial diagnosis

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