DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer

Müller, Dalma; Győrffy, Balázs

doi:10.1016/j.bbcan.2022.188722

Cited by 79 publications

(69 citation statements)

References 202 publications

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“…DNA methylation, characterized as a methyl group added to cytosines in cytosine-guanine (CpG) dinucleotides, is one of the key epigenetic modifications involved in the regulation of gene expression ( Müller and Győrffy, 2022 ). An existing body of evidence indicates that aberrant DNA methylation leads to activation of oncogenes and silencing of tumor suppressor genes, contributing to tumorigenesis and progression ( Klutstein et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Peng

et al. 2022

Front. Bioeng. Biotechnol.

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B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.

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Section: Discussionmentioning

confidence: 99%

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Peng

et al. 2022

Front. Bioeng. Biotechnol.

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“…However, they affect the structure and stability of DNA and play an important role in carcinogenesis. These epigenetic changes in cancer cells are therefore useful as cancer biomarkers, especially since DNA methylation changes occur in the early stages of tumorigenesis [ 16 ]. Loss of global DNA methylation is common in many tumors and is associated with genomic instability, DNA damage, and reactivation of transposons and retroviruses.…”

Section: Cancer-associated Alterationsmentioning

confidence: 99%

“…Moreover, more localized changes in DNA methylation at the CpG-rich promoter regions of the genes can inactivate tumor suppressor genes. For example, the CpG island methylator phenotype, characterized by hypermethylation of multiple sites, is a feature associated with genomic instability and cancer [ 16 ]. Methylation of CACN3A1G , IGF2 , NEUROG1 , RUNX3 , and SOCS1 promoters is common in this phenotype and is associated with MLH1 methylation and microsatellite instability.…”

Section: Cancer-associated Alterationsmentioning

confidence: 99%

“…Methylation of CACN3A1G , IGF2 , NEUROG1 , RUNX3 , and SOCS1 promoters is common in this phenotype and is associated with MLH1 methylation and microsatellite instability. It is noteworthy that MLH1 methylation is a biomarker used for cancer-prone Lynch syndrome testing in clinics [ 16 ]. In addition, DNA methylation biomarkers are also useful for predicting cancer treatment response; for example, tumor MGMT (gene important in DNA repair) promotor hypermethylation is associated with good response to alkylating drugs and used in clinical testing in glioblastomas [ 17 ].…”

Section: Cancer-associated Alterationsmentioning

confidence: 99%

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Molecular Biomarkers in Cancer

2022

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Molecular cancer biomarkers are any measurable molecular indicator of risk of cancer, occurrence of cancer, or patient outcome. They may include germline or somatic genetic variants, epigenetic signatures, transcriptional changes, and proteomic signatures. These indicators are based on biomolecules, such as nucleic acids and proteins, that can be detected in samples obtained from tissues through tumor biopsy or, more easily and non-invasively, from blood (or serum or plasma), saliva, buccal swabs, stool, urine, etc. Detection technologies have advanced tremendously over the last decades, including techniques such as next-generation sequencing, nanotechnology, or methods to study circulating tumor DNA/RNA or exosomes. Clinical applications of biomarkers are extensive. They can be used as tools for cancer risk assessment, screening and early detection of cancer, accurate diagnosis, patient prognosis, prediction of response to therapy, and cancer surveillance and monitoring response. Therefore, they can help to optimize making decisions in clinical practice. Moreover, precision oncology is needed for newly developed targeted therapies, as they are functional only in patients with specific cancer genetic mutations, and biomarkers are the tools used for the identification of these subsets of patients. Improvement in the field of cancer biomarkers is, however, needed to overcome the scientific challenge of developing new biomarkers with greater sensitivity, specificity, and positive predictive value.

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“…Although fewer mutations were found, the liver was correctly identified as the source of tumor-derived molecules. Hence, the methylation modification of cell DNA can be used as a biomarker in many clinical fields such as non-invasive prenatal testing, early cancer screening, early diagnosis, and organ transplantation evaluation ( Muller and Gyorffy, 2022 ; Zeng et al, 2022 ).…”

Section: Clinical Application Of Next-generation Sequencing Technologymentioning

confidence: 99%

Cancer Risk and Mutational Patterns Following Organ Transplantation

Shen

Lian

Shi

et al. 2022

Front. Cell Dev. Biol.

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The rapid development of medical technology and widespread application of immunosuppressive drugs have improved the success rate of organ transplantation significantly. However, the use of immunosuppressive agents increases the frequency of malignancy greatly. With the prospect of “precision medicine” for tumors and development of next-generation sequencing technology, more attention has been paid to the application of high-throughput sequencing technology in clinical oncology research, which is mainly applied to the early diagnosis of tumors and analysis of tumor-related genes. All generations of cancers carry somatic mutations, meanwhile, significant differences were observed in mutational signatures across tumors. Systematic sequencing of cancer genomes from patients after organ transplantation can reveal DNA damage and repair processes in exposed cancer cells and their precursors. In this review, we summarize the application of high-throughput sequencing and organoids in the field of organ transplantation, the mutational patterns of cancer genomes, and propose a new research strategy for understanding the mechanism of cancer following organ transplantation.

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DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer

Cited by 79 publications

References 202 publications

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Molecular Biomarkers in Cancer

Cancer Risk and Mutational Patterns Following Organ Transplantation

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