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Mini Review - (2022) Volume 13, Issue 9

Challenges in Promoter Methylation Research by Translational Oncology

Lucia Agarwal*
 
Department of Oncology, University of Hospital Zurich, Switzerland
 
*Correspondence: Lucia Agarwal, Department of Oncology, University of Hospital Zurich, Switzerland, Email:

Received: 01-Sep-2022, Manuscript No. Iptb- 22-13099; Editor assigned: 05-Sep-2022, Pre QC No. Iptb- 22-13099; Reviewed: 19-Sep-2022, QC No. Iptb- 22-13099; Revised: 23-Sep-2022, Manuscript No. Iptb- 22-13099 (R); Published: 30-Sep-2022

Abstract

Epigenetic changes have frequently been suggested for the diagnosis and creation of anti-cancer therapy techniques in the search for novel trustworthy biomarkers [1]. In fact, promoter methylation has to be paired with a highly informative technology that is tested in a suitable biospecimens for it to actively become a tumour marker for therapeutic application [2]. In fact, one of the most difficult issues in epigenetic research is methodological uniformity [3]. Additionally, liquid biopsy is being used to supplement and, in some situations, replace tissue-based biopsy [4]. This study will emphasise the improvements made for the prospective use of methylation biomarkers in clinical settings, with a focus on liquid biopsy, for both pre-analytical and analytical application [5]. With the assistance of active interaction with the milieu that makes up the tumour niche, the carcinogenic process progresses through the continuous accumulation of genetic and epigenetic changes that allow it to elude physiological regulation systems [5].

Keywords

Promoter hyper-methylation; Cancer biomarkers; Liquid biopsy

Introduction

Unquestionably, epigenetics is a second information layer that controls the information flow from the DNA and may specify the precise identity of each cell type [6]. This fine-tuned system is primarily supported by four pillars, including non-coding RNAs, histone posttranslational modifications HPTM, DNA methylation levels, and three-dimensional 3D chromatin architecture [7]. It is important to find anomalies in the epigenetic landscape linked to human disorders because epigenetic changes are coordinated events that influence transcription. In reality, it would offer fresh indicators needed to improve clinical judgement [8]. One of the earliest abnormalities to be observed during the development of a tumour mass is epigenetic modification. Furthermore, these pathways are usually bidirectional and reversible, making them desirable molecular drivers for the selection of therapeutic treatments and the assessment of response rate, survival, and time to therapy failure—all crucial components of emerging precision medicine [9]. This review's objective is to investigate the difficulties and potential applications of promoter methylation as a cancer diagnostic in clinical settings [10]. The methylation of cytosine’s in Chg [11]. Dinucleotides are undoubtedly the best researched of the four epigenetic foundations that can be changed during carcinogenesis [12]. The human genome has an uneven distribution of Chg. sites; whereas the majority of the genome has few and methylated Coggs, there are certain regions with high Chg density [13]. Transposable elements, centromeres, and oncogenes frequently experience DNA hypo methylation events, which increase aneuploidy and genomic instability; focal Tumor suppressor genes are silenced by cis-regulatory regions that may be identified by their Chg [14]. hyper methylation. DNA methylation is a reversible alteration that can alter tumour biology or characterise it. Since both global modifications to normal DNA methylation patterns and the methylation levels of regulatory regions are altered during the early stages of carcinogenesis, DNA methylation is undoubtedly the primary driver of tumorigenesis. These pathways interfere with apoptotic signals and promote cancer in combination with somatic driver mutations [15]. Additionally, modifications in DNA methylation control a variety of aspects of the pathophysiology of advanced stages of cancer, including responses to therapy and metastatization. The internal processes causing alterations in the pattern of 5-methylcytosine throughout the genome as a cause or result of cancer evolution are thus yet unknown despite the volume of study in this area. Promoter methylation analysis has been often suggested in this regard as a diagnostic for the detection of cancer and the creation of cancer treatment plans. DNA methylation is really a binary marker that can provide important details about how particular genes function in various cell types. It is more stable than RNAbased biomarkers, resilient against transitory perturbations, and does not need specific processing .DNA methylation can emphasise information on the progression of the disease because it mimics the interplay with the microenvironment, serving as a bio-archive. The O6 methyl guanine-DNA methyltransferase DNA repair gene is unquestionably the first promoter methylationrelated biomarker to be discovered. Glioblastomas with MGMT promoter hyper methylation are present in around 50% of cases. According to a number of clinical studies, Temozolomide and other alkylating medication regimens show a considerable benefit for patients with MGMT promoter hyper methylation. In order to manage patients with glioma burden, tests targeting MGMT promoter hyper methylation have become the norm, and are a key factor in determining the most effective treatment plan. This is one of the first assays to be marketed due to the wealth of scientific evidence backing it, despite the fact that there is no unanimity in the approach, which ranges from strictly qualitative to quantitative ones. Promoter methylation may be relevant to at least four macro-areas of interest.

Discussion

Early diagnosis: locating people who need to receive therapy and are impacted by a neoplasm. Treatment options: Promoter methylation analysis can serve as a predictive marker and identify malignancies that can benefit from first-line or alternative treatments. Promoter methylation analysis can be used to assess treatment response or the potential for the establishment of resistance. The methylation of cytosine in chg. dinucleotides is undoubtedly the best researched of the four epigenetic foundations that can be changed during carcinogenesis. The human genome has an uneven distribution of chg. sites; whereas the majority of the genome is composed of sparse, methylated Coggs, there are certain regions with a high chg. density known as pg. islands, which make up roughly 2% of the genome. Tumour suppressor gene silencing DNA methylation is a reversible alteration that can characterise or accommodate tumour biology. Since both global modifications to normal DNA methylation patterns and the methylation levels of regulatory regions are altered during the early stages of carcinogenesis, DNA methylation is undoubtedly the primary driver of tumorigenesis. These pathways interfere with apoptotic signals and promote cancer in combination with somatic driver mutations. Additionally, modifications in DNA methylation control a variety of aspects of the pathophysiology of advanced stages of cancer, including responses to therapy and metastatization. Following therapies like surgery, adjuvant chemotherapy, or radiation, minimum residual disease is monitored to identify individuals who are more likely to have recurrence. It has become clearer that aberrant DNA methylation would be of translational relevance over time since it might potentially lead to a viable method for cancer diagnosis by contributing to the very early stages of carcinogenesis. Because there are few recurring mutations in early-stage carcinomas and because tumour tissue is clonal and heterogeneous, screening approaches based on mutation detection have low sensitivity. DNA methylation, on the other hand, is less molecularly limited, and hence, the associated tests are better able to identify cancer in its early stages. Additionally, cancer cells have tissue-specific DNA methylation patterns that are pervasive across the tumour mass in comparison to normal cells. In accordance with the same logic, DNA methylation-based indicators might indicate the presence of minor residual illness before any with the assistance of active interaction with the milieu that makes up the tumour niche, the carcinogenic process progresses through the continuous accumulation of genetic and epigenetic changes that allow it to elude physiological regulation mechanisms. Unquestionably, epigenetics is a second information layer that controls the information flow from the DNA and may specify the precise identity of each cell type. The four foundations of this finely controlled system are non-coding RNAs, histone post-translational modifications HPTM, DNA methylation levels, and three-dimensional 3D chromatin architecture. It is important to find anomalies in the epigenetic landscape linked to human disorders because epigenetic changes are coordinated events that influence transcription. In reality, it would offer fresh indicators needed to improve clinical judgement. With the help of active interaction with the milieu that makes up the tumour niche, the carcinogenic process progresses through the continuous accumulation of genetic and epigenetic changes that allow it to elude physiological regulation systems. Without a doubt, epigenetics is a second information layer that controls the information flow from the genome and may determine the true identity of each cell type. Four pillars DNA methylation levels, histone post-translational modifications, non-coding RNAs, and three-dimensional 3D chromatin organization—form the foundation of this finely calibrated process.

Conclusion

It is important to find anomalies in the epigenetic landscape linked to human disorders because epigenetic changes are coordinated events that influence transcription. In reality, it would offer fresh indicators needed to improve clinical judgement. Epigenetic Furthermore, these pathways are usually bidirectional and reversible, making them desirable molecular drivers for the selection of therapeutic treatments and the assessment of response rate, survival, and time to therapy failure all crucial components of emerging precision medicine. This review's objective is to investigate the difficulties and potential applications of promoter methylation as a cancer diagnostic in clinical settings. Tumor-related DNA methylation. The methylation of cytosine in pg. dinucleotides is undoubtedly the best researched of the four epigenetic foundations that can be changed during carcinogenesis. Human CpG sites are not distributed uniformly. DNA methylation is a reversible alteration that can characterise or accommodate tumour biology. Since both global modifications to normal DNA methylation patterns and the methylation levels of regulatory regions are altered during the early stages of carcinogenesis, DNA methylation is undoubtedly the primary driver of tumorigenesis. These pathways interfere with apoptotic signals and promote cancer in combination with somatic driver mutations. Additionally, modifications in DNA methylation control a variety of aspects of the pathophysiology of advanced stages of cancer, including responses to therapy and metastatization. The internal processes causing alterations in the pattern of 5-methylcytosine throughout the genome as a cause or result of cancer evolution are thus yet unknown despite the volume of study in this area.

Acknowledgement

None

Conflict of Interest

None

References

  1. Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128: 635-638.
  2. Indexed at, Crossref, Google Scholar

  3. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33: 245-254.
  4. Indexed at, Crossref, Google Scholar

  5. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447: 433-440.
  6. Indexed at, Crossref, Google Scholar

  7. Anderson OS, Sant KE, Dolinoy DC (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23: 853-859.
  8. Indexed at, Google Scholar

  9. Bjornsson HT, Fallin MD, Feinberg AP (2004) An integrated epigenetic and genetic approach to common human disease. Trends Gen 20: 350-358.
  10. Indexed at, Crossref, Google Scholar

  11. Ladd Acosta C (2015) Epigenetic signatures as biomarkers of exposure. Curr Environ Health Rep 2: 117-125.
  12. Indexed at, Crossref, Google Scholar

  13. Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, et al. (2014)DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 5: 5592.
  14. Indexed at, Crossref, Google Scholar

  15. Rodenhiser D, Mann M (2006) Epigenetics and human disease: translating basic biology into clinical applications. Can Med Assoc J 174: 341-348.
  16. Indexed at, Crossref, Google Scholar

  17. Hsieh J, Eisch AJ (2010) Epigenetics, hippocampal neurogenesis, and neuropsychiatric disorders: Unraveling the genome to understand the mind. Neurobiol Dis 39: 73-84.
  18. Indexed at, Crossref, Google Scholar

  19. Sweatt JD (2013) The emerging field of neuroepigenetics. Neuron 80: 624-632.
  20. Indexed at, Crossref, Google Scholar

  21. Loke YJ, Hannan AJ, Craig JM (2015) The Role of Epigenetic Change in Autism Spectrum Disorders. Front Neurol 6: 107.
  22. Indexed at, Crossref, Google Scholar

  23. Abdolmaleky HM, Zhou JR, Thiagalingam S (2015) An update on the epigenetics of psychotic diseases and autism. Epigenomics 7: 427-449.
  24. Indexed at, Crossref, Google Scholar

  25. Ibi D, Gonzalez Maeso J (2015) Epigenetic signaling in schizophrenia. Cell Signal 27: 2131-2136.
  26. Indexed at, Crossref, Google Scholar

  27. Shorter KR, Miller BH (2015) Epigenetic mechanisms in schizophrenia. Prog Biophys Mol Biol 1181: 1-7.
  28. Indexed at, Crossref, Google Scholar

  29. Vinkers CH, Kalafateli AL, Rutten BP, Kas MJ, Kaminsky Z, et al. Traumatic stress and human DNA methylation: a critical review. Epigenomics 7: 593-608.
  30. Indexed at, Crossref, Google Scholar

Keywords

Promoter hyper-methylation; Cancer biomarkers; Liquid biopsy

Introduction

Unquestionably, epigenetics is a second information layer that controls the information flow from the DNA and may specify the precise identity of each cell type [6]. This fine-tuned system is primarily supported by four pillars, including non-coding RNAs, histone posttranslational modifications HPTM, DNA methylation levels, and three-dimensional 3D chromatin architecture [7]. It is important to find anomalies in the epigenetic landscape linked to human disorders because epigenetic changes are coordinated events that influence transcription. In reality, it would offer fresh indicators needed to improve clinical judgement [8]. One of the earliest abnormalities to be observed during the development of a tumour mass is epigenetic modification. Furthermore, these pathways are usually bidirectional and reversible, making them desirable molecular drivers for the selection of therapeutic treatments and the assessment of response rate, survival, and time to therapy failure—all crucial components of emerging precision medicine [9]. This review's objective is to investigate the difficulties and potential applications of promoter methylation as a cancer diagnostic in clinical settings [10]. The methylation of cytosine’s in Chg [11]. Dinucleotides are undoubtedly the best researched of the four epigenetic foundations that can be changed during carcinogenesis [12]. The human genome has an uneven distribution of Chg. sites; whereas the majority of the genome has few and methylated Coggs, there are certain regions with high Chg density [13]. Transposable elements, centromeres, and oncogenes frequently experience DNA hypo methylation events, which increase aneuploidy and genomic instability; focal Tumor suppressor genes are silenced by cis-regulatory regions that may be identified by their Chg [14]. hyper methylation. DNA methylation is a reversible alteration that can alter tumour biology or characterise it. Since both global modifications to normal DNA methylation patterns and the methylation levels of regulatory regions are altered during the early stages of carcinogenesis, DNA methylation is undoubtedly the primary driver of tumorigenesis. These pathways interfere with apoptotic signals and promote cancer in combination with somatic driver mutations [15]. Additionally, modifications in DNA methylation control a variety of aspects of the pathophysiology of advanced stages of cancer, including responses to therapy and metastatization. The internal processes causing alterations in the pattern of 5-methylcytosine throughout the genome as a cause or result of cancer evolution are thus yet unknown despite the volume of study in this area. Promoter methylation analysis has been often suggested in this regard as a diagnostic for the detection of cancer and the creation of cancer treatment plans. DNA methylation is really a binary marker that can provide important details about how particular genes function in various cell types. It is more stable than RNAbased biomarkers, resilient against transitory perturbations, and does not need specific processing .DNA methylation can emphasise information on the progression of the disease because it mimics the interplay with the microenvironment, serving as a bio-archive. The O6 methyl guanine-DNA methyltransferase DNA repair gene is unquestionably the first promoter methylationrelated biomarker to be discovered. Glioblastomas with MGMT promoter hyper methylation are present in around 50% of cases. According to a number of clinical studies, Temozolomide and other alkylating medication regimens show a considerable benefit for patients with MGMT promoter hyper methylation. In order to manage patients with glioma burden, tests targeting MGMT promoter hyper methylation have become the norm, and are a key factor in determining the most effective treatment plan. This is one of the first assays to be marketed due to the wealth of scientific evidence backing it, despite the fact that there is no unanimity in the approach, which ranges from strictly qualitative to quantitative ones. Promoter methylation may be relevant to at least four macro-areas of interest.

Discussion

Early diagnosis: locating people who need to receive therapy and are impacted by a neoplasm. Treatment options: Promoter methylation analysis can serve as a predictive marker and identify malignancies that can benefit from first-line or alternative treatments. Promoter methylation analysis can be used to assess treatment response or the potential for the establishment of resistance. The methylation of cytosine in chg. dinucleotides is undoubtedly the best researched of the four epigenetic foundations that can be changed during carcinogenesis. The human genome has an uneven distribution of chg. sites; whereas the majority of the genome is composed of sparse, methylated Coggs, there are certain regions with a high chg. density known as pg. islands, which make up roughly 2% of the genome. Tumour suppressor gene silencing DNA methylation is a reversible alteration that can characterise or accommodate tumour biology. Since both global modifications to normal DNA methylation patterns and the methylation levels of regulatory regions are altered during the early stages of carcinogenesis, DNA methylation is undoubtedly the primary driver of tumorigenesis. These pathways interfere with apoptotic signals and promote cancer in combination with somatic driver mutations. Additionally, modifications in DNA methylation control a variety of aspects of the pathophysiology of advanced stages of cancer, including responses to therapy and metastatization. Following therapies like surgery, adjuvant chemotherapy, or radiation, minimum residual disease is monitored to identify individuals who are more likely to have recurrence. It has become clearer that aberrant DNA methylation would be of translational relevance over time since it might potentially lead to a viable method for cancer diagnosis by contributing to the very early stages of carcinogenesis. Because there are few recurring mutations in early-stage carcinomas and because tumour tissue is clonal and heterogeneous, screening approaches based on mutation detection have low sensitivity. DNA methylation, on the other hand, is less molecularly limited, and hence, the associated tests are better able to identify cancer in its early stages. Additionally, cancer cells have tissue-specific DNA methylation patterns that are pervasive across the tumour mass in comparison to normal cells. In accordance with the same logic, DNA methylation-based indicators might indicate the presence of minor residual illness before any with the assistance of active interaction with the milieu that makes up the tumour niche, the carcinogenic process progresses through the continuous accumulation of genetic and epigenetic changes that allow it to elude physiological regulation mechanisms. Unquestionably, epigenetics is a second information layer that controls the information flow from the DNA and may specify the precise identity of each cell type. The four foundations of this finely controlled system are non-coding RNAs, histone post-translational modifications HPTM, DNA methylation levels, and three-dimensional 3D chromatin architecture. It is important to find anomalies in the epigenetic landscape linked to human disorders because epigenetic changes are coordinated events that influence transcription. In reality, it would offer fresh indicators needed to improve clinical judgement. With the help of active interaction with the milieu that makes up the tumour niche, the carcinogenic process progresses through the continuous accumulation of genetic and epigenetic changes that allow it to elude physiological regulation systems. Without a doubt, epigenetics is a second information layer that controls the information flow from the genome and may determine the true identity of each cell type. Four pillars DNA methylation levels, histone post-translational modifications, non-coding RNAs, and three-dimensional 3D chromatin organization—form the foundation of this finely calibrated process.

Conclusion

It is important to find anomalies in the epigenetic landscape linked to human disorders because epigenetic changes are coordinated events that influence transcription. In reality, it would offer fresh indicators needed to improve clinical judgement. Epigenetic Furthermore, these pathways are usually bidirectional and reversible, making them desirable molecular drivers for the selection of therapeutic treatments and the assessment of response rate, survival, and time to therapy failure all crucial components of emerging precision medicine. This review's objective is to investigate the difficulties and potential applications of promoter methylation as a cancer diagnostic in clinical settings. Tumor-related DNA methylation. The methylation of cytosine in pg. dinucleotides is undoubtedly the best researched of the four epigenetic foundations that can be changed during carcinogenesis. Human CpG sites are not distributed uniformly. DNA methylation is a reversible alteration that can characterise or accommodate tumour biology. Since both global modifications to normal DNA methylation patterns and the methylation levels of regulatory regions are altered during the early stages of carcinogenesis, DNA methylation is undoubtedly the primary driver of tumorigenesis. These pathways interfere with apoptotic signals and promote cancer in combination with somatic driver mutations. Additionally, modifications in DNA methylation control a variety of aspects of the pathophysiology of advanced stages of cancer, including responses to therapy and metastatization. The internal processes causing alterations in the pattern of 5-methylcytosine throughout the genome as a cause or result of cancer evolution are thus yet unknown despite the volume of study in this area.

Acknowledgement

None

Conflict of Interest

None

References

  1. Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128: 635-638.
  2. Indexed at, Crossref, Google Scholar

  3. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33: 245-254.
  4. Indexed at, Crossref, Google Scholar

  5. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447: 433-440.
  6. Indexed at, Crossref, Google Scholar

  7. Anderson OS, Sant KE, Dolinoy DC (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23: 853-859.
  8. Indexed at, Google Scholar

  9. Bjornsson HT, Fallin MD, Feinberg AP (2004) An integrated epigenetic and genetic approach to common human disease. Trends Gen 20: 350-358.
  10. Indexed at, Crossref, Google Scholar

  11. Ladd Acosta C (2015) Epigenetic signatures as biomarkers of exposure. Curr Environ Health Rep 2: 117-125.
  12. Indexed at, Crossref, Google Scholar

  13. Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, et al. (2014)DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 5: 5592.
  14. Indexed at, Crossref, Google Scholar

  15. Rodenhiser D, Mann M (2006) Epigenetics and human disease: translating basic biology into clinical applications. Can Med Assoc J 174: 341-348.
  16. Indexed at, Crossref, Google Scholar

  17. Hsieh J, Eisch AJ (2010) Epigenetics, hippocampal neurogenesis, and neuropsychiatric disorders: Unraveling the genome to understand the mind. Neurobiol Dis 39: 73-84.
  18. Indexed at, Crossref, Google Scholar

  19. Sweatt JD (2013) The emerging field of neuroepigenetics. Neuron 80: 624-632.
  20. Indexed at, Crossref, Google Scholar

  21. Loke YJ, Hannan AJ, Craig JM (2015) The Role of Epigenetic Change in Autism Spectrum Disorders. Front Neurol 6: 107.
  22. Indexed at, Crossref, Google Scholar

  23. Abdolmaleky HM, Zhou JR, Thiagalingam S (2015) An update on the epigenetics of psychotic diseases and autism. Epigenomics 7: 427-449.
  24. Indexed at, Crossref, Google Scholar

  25. Ibi D, Gonzalez Maeso J (2015) Epigenetic signaling in schizophrenia. Cell Signal 27: 2131-2136.
  26. Indexed at, Crossref, Google Scholar

  27. Shorter KR, Miller BH (2015) Epigenetic mechanisms in schizophrenia. Prog Biophys Mol Biol 1181: 1-7.
  28. Indexed at, Crossref, Google Scholar

  29. Vinkers CH, Kalafateli AL, Rutten BP, Kas MJ, Kaminsky Z, et al. Traumatic stress and human DNA methylation: a critical review. Epigenomics 7: 593-608.
  30. Indexed at, Crossref, Google Scholar

Citation: Agarwal L (2022) Challenges in Promoter Methylation Research by Translational Oncology. Transl Biomed, Vol. 13 No. 9: 254.