Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors

Kuo, Lu-Ting; Lu, Hsueh Yi; Lee, Chien‐Chang; Tsai, Jui‐Chang; Lai, Hong‐Shiee; Tseng, Ham Min; Kuo, Meng-Fai; Tu, Yong Kwang

doi:10.1002/cam4.762

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…Recent data implicate that in ER-positive tumors, CpG methylation levels are inversely correlated with ER expression status, suggesting that single CpG site plays an important role in the regulation of ER transcription (24). Many studies are focused on ESR1 methylation in various cancer types (25)(26)(27)(28)(29), but only a limited number proves a clinical relevance in terms of diagnosis (30), prognosis (31), and response to therapy (32).…”

Section: Introductionmentioning

confidence: 99%

ESR1 Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment

Mastoraki

Strati

Tzanikou

et al. 2018

Clinical Cancer Research

137

113

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Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). epigenetic silencing potentially affects response to endocrine treatment. We evaluated methylation in CTCs and paired plasma ctDNA. We evaluated methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. A highly sensitive and specific real-time MSP assay for methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER/HER2 advanced breast cancer receiving everolimus/exemestane. methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) : 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) 8/108 (7.4%) patients and 1/30 (3.3%) HD. methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment ( = 0.023, Fisher exact test). We report for the first time the detection of methylation in CTCs and a high concordance with paired plasma ctDNA. methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. methylation should be further evaluated as a potential liquid biopsy-based biomarker..

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Section: Introductionmentioning

confidence: 99%

ESR1 Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment

Mastoraki

Strati

Tzanikou

et al. 2018

Clinical Cancer Research

137

113

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“…Aberrant methylation was identified by the appearance of a signal peak after HhaI enzyme digestion, and methylation was scored when the calculated ratio compared with normal unmethylated loci was more than 15%. 43 …”

Section: Methodsmentioning

confidence: 99%

Hemizygous deletion of cyclin-dependent kinase inhibitor 2A/B with p16 immuno-negative and methylthioadenosine phosphorylase retention predicts poor prognosis in IDH-mutant adult glioma

Otsuji,

Hata,

Yamamoto

et al. 2024

Neuro-Oncology Advances

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Background Homozygous deletion of the tumor suppression genes cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is a strong adverse prognostic factor in IDH-mutant gliomas, particularly astrocytoma. However, the impact of hemizygous deletion of CDKN2A/B is unknown. Furthermore, the influence of CDKN2A/B status in IDH-mutant and 1p/19q-codeleted oligodendroglioma remains controversial. We examined the impact of CDKN2A/B status classification, including hemizygous deletions, on the prognosis of IDH-mutant gliomas. Methods We enrolled 101 adults with IDH-mutant glioma between December 2002 and November 2021. CDKN2A/B deletion was evaluated with multiplex ligation-dependent probe amplification (MLPA). Immunohistochemical analysis of p16/MTAP and promoter methylation analysis with methylation-specific MLPA was performed for cases with CDKN2A/B deletion. Kaplan−Meier plots and Cox proportion hazards model analyses were performed to evaluate the impact on overall (OS) and progression-free survival. Results Of 101 cases, 12 and 4 were classified as hemizygous and homozygous deletion, respectively. Immunohistochemistry revealed p16-negative and MTAP retention in cases with hemizygous deletion, whereas homozygous deletions had p16-negative and MTAP loss. In astrocytoma, OS was shorter in the order of homozygous deletion, hemizygous deletion, and copy-neutral groups (median OS: 38.5, 59.5, and 93.1 months, respectively). Multivariate analysis revealed hazard ratios of 9.30 (p=0.0191) and 2.44 (p=0.0943) for homozygous and hemizygous deletions, respectively. Conclusions CDKN2A/B hemizygous deletions exerted a negative impact on OS in astrocytoma. Immunohistochemistry of p16/MTAP can be utilized to validate hemizygous or homozygous deletions in combination with conventional molecular diagnosis.

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“…Great efforts have been made to identify molecular markers for prognostic prediction. Many recent studies have focused on gene expression profiles in glioma to construct signatures 5–10 , which have shown great promise for prognostic prediction in individual patients. However, the limitation of the gene selection method, which uses formula designation for application within different platforms, is also obvious.…”

Section: Introductionmentioning

confidence: 99%

Astrocytoma progression scoring system based on the WHO 2016 criteria

Guan

Liu

et al. 2019

Sci Rep

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Diffuse astrocytoma (including glioblastoma) is morbid with a worse prognosis than other types of glioma. Therefore, we sought to build a progression-associated score to improve malignancy and prognostic predictions for astrocytoma. The astrocytoma progression (AP) score was constructed through bioinformatics analyses of the training cohort (TCGA RNA-seq) and included 18 genes representing distinct aspects of regulation during astrocytoma progression. This classifier could successfully discriminate patients with distinct prognoses in the training and validation (REMBRANDT, GSE16011 and TCGA-GBM Microarray) cohorts (P < 0.05 in all cohorts) and in different clinicopathological subgroups. Distinct patterns of somatic mutations and copy number variation were also observed. The bioinformatics analyses suggested that genes associated with a higher AP score were significantly involved in cancer progression-related biological processes, such as the cell cycle and immune/inflammatory responses, whereas genes associated with a lower AP score were associated with relatively normal nervous system biological processes. The analyses indicated that the AP score was a robust predictor of patient survival, and its ability to predict astrocytoma malignancy was well elucidated. Therefore, this bioinformatics-based scoring system suggested that astrocytoma progression could distinguish patients with different underlying biological processes and clinical outcomes, facilitate more precise tumour grading and possibly shed light on future classification strategies and therapeutics for astrocytoma patients.

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Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors

Cited by 8 publications

References 33 publications

ESR1 Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment

ESR1 Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment

Hemizygous deletion of cyclin-dependent kinase inhibitor 2A/B with p16 immuno-negative and methylthioadenosine phosphorylase retention predicts poor prognosis in IDH-mutant adult glioma

Astrocytoma progression scoring system based on the WHO 2016 criteria

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