A DNA methylation-based liquid biopsy for triple-negative breast cancer

Cristall, Katrina; Bidard, François‐Clément; Pierga, Jean‐Yves; Rauh, Michael J.; Popova, Tatiana; Sebbag, Clara; Lantz, Olivier; Stern, Marc‐Henri; Mueller, Christopher R.

doi:10.1038/s41698-021-00198-9

Cited by 16 publications

(12 citation statements)

References 77 publications

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“…Here, we performed a head-to-head comparison between methylome analyses results derived from serum and plasma cfDNA and observed that these 2 sources of DNA are different in several aspects, such as cell composition estimations and genome-wide and supervised mean methylation levels; however, they both provided unique or common PitNET-specific markers that were able to differentiate PitNETs from other tumors, suggesting that the use of either blood element is useful, and possibly complementary, as a noninvasive methylation-based diagnostic tool ( Supplementary Figure S2C ; Supplementary File S5 ). 45 , 46 …”

Section: Discussionmentioning

confidence: 99%

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors

et al. 2022

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Background DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system tumors but not across PitNETs. The aim of the study was to use the liquid biopsy approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. Method We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma liquid biopsy specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas and skull base meningiomas) or nontumor conditions, grouped as non-PitNET. Results Our results indicated that, despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of liquid biopsy showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, liquid biopsy methylomes captured epigenetic features reported in PitNET tissue and provided information about cell type composition. Using liquid biopsy-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores which distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. Conclusions Our results underpin the potential application of methylation-based liquid biopsy profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

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Section: Discussionmentioning

confidence: 99%

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors

et al. 2022

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“…Several markers have been previously shown to be associated with BC. 9,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] The protein kinase CDKL2 was reported to be hypermethylated in HER2-positive BC tissues compared to normal breast tissues. 40 Its differential methylation was associated with response to neoadjuvant chemotherapy in patients with TNBC.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study on metastatic TNBC, an AUC of 0.92 was reported using a next-generation sequencing (NGS) methylation-based blood test. 32 In another study, a DNA methylationbased epigenetic signature of breast DNA was described using three methylation markers. 43 The later study was performed on plasma samples of BC patients with metastatic and localized disease and reported an AUC of 0.9 and 0.91, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Of those, C2CD4D , KIAA1949 , IFFO1 , TXNRD1 , OTX2 , PPP1R16B , PRDM16 and ALPL , were associated with several other malignancies including neuroblastoma, 20 ovarian, 21 lung, 22 esophageal, 23 and prostate 24 cancers. Several markers have been previously shown to be associated with BC 9,25‐39 . The protein kinase CDKL2 was reported to be hypermethylated in HER2‐positive BC tissues compared to normal breast tissues 40 .…”

Section: Discussionmentioning

confidence: 99%

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DNA methylation biomarkers for noninvasive detection of triple‐negative breast cancer using liquid biopsy

Manoochehri

Borhani

Gerhäuser

et al. 2022

Intl Journal of Cancer

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Noninvasive detection of aberrant DNA methylation could provide invaluable biomarkers for earlier detection of triple‐negative breast cancer (TNBC) which could help clinicians with easier and more efficient treatment options. We evaluated genome‐wide DNA methylation data derived from TNBC and normal breast tissues, peripheral blood of TNBC cases and controls and reference samples of sorted blood and mammary cells. Differentially methylated regions (DMRs) between TNBC and normal breast tissues were stringently selected, verified and externally validated. A machine‐learning algorithm was applied to select the top DMRs, which then were evaluated on plasma‐derived circulating cell‐free DNA (cfDNA) samples of TNBC patients and healthy controls. We identified 23 DMRs accounting for the methylation profile of blood cells and reference mammary cells and then selected six top DMRs for cfDNA analysis. We quantified un‐/methylated copies of these DMRs by droplet digital PCR analysis in a plasma test set from TNBC patients and healthy controls and confirmed our findings obtained on tissues. Differential cfDNA methylation was confirmed in an independent validation set of plasma samples. A methylation score combining signatures of the top three DMRs overlapping with the SPAG6, LINC10606 and TBCD/ZNF750 genes had the best capability to discriminate TNBC patients from controls (AUC = 0.78 in the test set and AUC = 0.74 in validation set). Our findings demonstrate the usefulness of cfDNA‐based methylation signatures as noninvasive liquid biopsy markers for the diagnosis of TNBC.

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“…DNA methylation is an epigenetic modification that is associated with regulating cell differentiation and tissue development ( Smith and Meissner, 2013 ; Slieker et al, 2015 ). Dysregulation of DNA methylation patterns are important characteristics of several diseases, including cancers ( Li et al, 2013 ; Božić et al, 2021 ; Cristall et al, 2021 ; Miyakuni et al, 2021 ). 5-Methylcytosine (5mC), a type of DNA methylation, was firstly reported by Wyatt, (1951) .…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer

Liu

Guo

Liu

et al. 2021

Front. Cell Dev. Biol.

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Background: DNA methylation is an important epigenetic modification, among which 5-methylcytosine methylation (5mC) is generally associated with tumorigenesis. Nonetheless, the potential roles of 5mC regulators in the tumor microenvironment (TME) remain unclear.Methods: The 5mC modification patterns of 1,374 lung adenocarcinoma samples were analyzed systematically. The correlation between the 5mC modification and tumor microenvironment cell infiltration was further assessed. The 5mCscore was developed to evaluate tumor mutation burden, immune check-point inhibitor response, and the clinical prognosis of individual tumors.Results: Three 5mC modification patterns were established based on the clinical characteristics of 21 5mC regulators. According to the differential expression of 5mC regulators, three distinct 5mC gene cluster were also identified, which showed distinct TME immune cell infiltration patterns and clinical prognoses. The 5mCscore was constructed to evaluate the tumor mutation burden, immune check-point inhibitor response, and prognosis characteristics. We found that patients with a low 5mCscore had significant immune cell infiltration and increased clinical benefit.Conclusion: This study indicated that the 5mC modification is involved in regulating TME infiltration remodeling. Targeting 5mC modification regulators might be a novel strategy to treat lung cancer.

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A DNA methylation-based liquid biopsy for triple-negative breast cancer

Cited by 16 publications

References 77 publications

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors

DNA methylation biomarkers for noninvasive detection of triple‐negative breast cancer using liquid biopsy

Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer

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