Quantitative analysis of CDKN2A methylation, mRNA, and p16INK4a protein expression in children and adolescents with Burkitt lymphoma: Biological and clinical implications

Robaina, Marcela Cristina; Faccion, Roberta Soares; Arruda, Viviane Oliveira; Rezende, Lídia Maria Magalhães de; Vasconcelos, Gisele M.; Apa, Alexandre Gustavo; Bacchi, Carlos E.; Klumb, Claudete Esteves

doi:10.1016/j.leukres.2014.11.023

Cited by 15 publications

(8 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Burkitt's lymphoma is a common subtype of B-cell non-Hodgkin's lymphoma in children and adolescents ( Molyneux et al, 2012 ). A recent analysis of 51 Burkitt's lymphoma tumor samples revealed that methylation of the CDKN2A promoter occurred in 72.5% of the samples and nuclear expression of the p16 INK4a protein remained undetectable in about 41% of the samples ( Robaina et al, 2015 ). In this study, CDKN2A promoter methylation was detected in 32 patient samples (80%) at stage III/IV of the cancer ( Robaina et al, 2015 ).…”

Section: Genetic Alterations Of Cdkn2a In Various mentioning

confidence: 99%

Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 INK4a ) in Cancer

et al. 2016

View full text Add to dashboard Cite

Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK) 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.

show abstract

Section: Genetic Alterations Of Cdkn2a In Various mentioning

confidence: 99%

Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 INK4a ) in Cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Burkitt lymphoma is characterized by the deregulation of DNA methylation switching certain tumor suppressor genes off [26][27][28]. Serine biosynthesis pathway is linked to the methionine cycle, responsible for the production of S-adenosylmethionine (SAM), a universal methyl group donor in cellular DNA and histone methylation reactions.…”

Section: Nct-503 Decreases Histone and Dna Methylation And Causes Re-mentioning

confidence: 99%

Serine Biosynthesis Pathway Supports MYC–miR-494–EZH2 Feed-Forward Circuit Necessary to Maintain Metabolic and Epigenetic Reprogramming of Burkitt Lymphoma Cells

Białopiotrowicz

Noyszewska‐Kania

Kachamakova‐Trojanowska

et al. 2020

Cancers

View full text Add to dashboard Cite

Burkitt lymphoma (BL) is a rapidly growing tumor, characterized by high anabolic requirements. The MYC oncogene plays a central role in the pathogenesis of this malignancy, controlling genes involved in apoptosis, proliferation, and cellular metabolism. Serine biosynthesis pathway (SBP) couples glycolysis to folate and methionine cycles, supporting biosynthesis of certain amino acids, nucleotides, glutathione, and a methyl group donor, S-adenosylmethionine (SAM). We report that BLs overexpress SBP enzymes, phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1). Both genes are controlled by the MYC-dependent ATF4 transcription factor. Genetic ablation of PHGDH/PSAT1 or chemical PHGDH inhibition with NCT-503 decreased BL cell lines proliferation and clonogenicity. NCT-503 reduced glutathione level, increased reactive oxygen species abundance, and induced apoptosis. Consistent with the role of SAM as a methyl donor, NCT-503 decreased DNA and histone methylation, and led to the re-expression of ID4, KLF4, CDKN2B and TXNIP tumor suppressors. High H3K27me3 level is known to repress the MYC negative regulator miR-494. NCT-503 decreased H3K27me3 abundance, increased the miR-494 level, and reduced the expression of MYC and MYC-dependent histone methyltransferase, EZH2. Surprisingly, chemical/genetic disruption of SBP did not delay BL and breast cancer xenografts growth, suggesting the existence of mechanisms compensating the PHGDH/PSAT1 absence in vivo.

show abstract

“…24 CDKN2A/B mutations were associated with elevated risk of diseases, such as coronary artery disease 25,26 and melanoma 27 ; and were frequent in the wide spectrum of human cancers. [28][29][30][31][32][33][34][35][36][37][38] In the current study we aimed to evaluate the simultaneous association of both SNP rs1801133 in MTHFR and rs10881661 in CDKN2A/B genes with the risk of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer

Hesari

Maleksabet

Tirkani

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

The 5,10‐Methylenetetrahydrofolate reductase (MTHFR) was the rate‐limiting enzyme in the methyl cycle, which was encoded by the MTHFR gene. MTHFR played a key role in homocysteine plasma level and was associated with the risk of breast cancer. The cyclin‐dependent kinase (CDK) inhibitor (CDKN2A/B) was the tumor suppressor in the cell cycle regulation. The single‐nucleotide polymorphism was thought to be associated with the predisposition of breast cancer and in subsequent immune response in different populations. The current study was conducted on a peripheral blood sample of 100 Iranian women with breast carcinoma and 142 cancer‐free healthy female volunteers. The TaqMan real‐time polymerase chain reaction technique was applied for genotyping of participants. The correlation of both variants and demographic data were investigated with the risk of breast cancer. Our data showed that the MTHFR allele T and TT genotype had the higher prevalence in patients (P < 0.0001) than the control group. The frequency of risk C allele into the CDKN2A/B rs10811661 was 72%. The correlations of menarche and underlying hormonal disorder with the risk of breast cancer were investigated; also our results showed that the menopause status was statistically significant between patients and controls (P = 0.036). Our investigations demonstrated that the MTHFR rs180113 and CDKN2A/B rs10811661 had a significant correlation with the elevated risk of breast cancer and they might be potentially valuable to apply as a prognostic factor for individual health care.

show abstract

Quantitative analysis of CDKN2A methylation, mRNA, and p16INK4a protein expression in children and adolescents with Burkitt lymphoma: Biological and clinical implications

Cited by 15 publications

References 55 publications

Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 INK4a ) in Cancer

Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 INK4a ) in Cancer

Serine Biosynthesis Pathway Supports MYC–miR-494–EZH2 Feed-Forward Circuit Necessary to Maintain Metabolic and Epigenetic Reprogramming of Burkitt Lymphoma Cells

Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer

Contact Info

Product

Resources

About