Methylation profiling of tumor suppressor genes

Histone modifications often work together with DNA methylation; however, how these epigenetic alterations regulate TSGs remains unclear. Methylation profiling revealed that four genes had very high frequencies of methylation in HCCs, but interestingly, similar high frequencies were also detected in corresponding noncancerous tissues We demonstrated that 3OST2 methylation may play a critical role in the earliest steps of hepatocarcinogenesis and is directly regulated by UHRF1.

Methylation profiling of tumor suppressor genes

Johnson Find articles by David C. Walker Find articles by Brian A. Wardell Find articles by Christopher P. Davies Find articles by Faith E. Morgan Find articles by Gareth J. Orsola-Malpighi, Bologna, Italy Corresponding author.

Received Mar 1; Accepted May 9. Key Points Epigenetic inactivation of tumor suppressor genes is associated with an unfavorable prognosis in multiple myeloma.

Drug response and microenvironment interaction pathways are affected by epigenetic inactivation, linking tumor biology to prognosis. Abstract Outcome in multiple myeloma is highly variable and a better understanding of the factors that influence disease biology is essential to understand and predict behavior in individual patients.

Methylation profiling of tumor suppressor genes

We used these data to identify epigenetically repressed tumor suppressor genes with prognostic relevance in myeloma. We identified genes with changes in methylation status that were significantly associated with prognosis. Hypermethylation of these genes was associated with significantly shorter overall survival, independent of age, International Staging System score, and adverse cytogenetics.

The 4 differentially methylated and expressed genes are known to mediate important tumor suppressive functions including response to chemotherapy TGFBIinteraction with the microenvironment SPARCretinoic acid signaling RBP1and the response to oxidative stress GPX3which could explain the prognostic impact of their differential methylation.

Assessment of the DNA methylation status of the identified genes could contribute to the molecular characterization of myeloma, which is prerequisite for an individualized treatment approach.

Methylation of tumor suppressor genes in ovarian cancer

Introduction It is becoming clearer that multiple myeloma MM is not a single disease but rather comprises multiple diseases with differences in outcome that are defined by their genetic makeup. The identification of factors that mediate these differences in disease biology is of central importance if we are to improve treatment outcome further.

To date there has been a focus on DNA changes such as translocations, copy number abnormalities, and mutational spectrum, but more recently the importance of epigenetic changes that affect myeloma cell biology has been realized.

We found specific, focal hypermethylation changes in clinically aggressive subtypes, such as plasma cell leukemia PCL and the prognostically unfavorable group with translocation t 4;14suggesting that methylation changes can affect disease biology and that further genes remain to be identified.

The identified epigenetically modified tumor suppressor genes may contribute to the molecular characterization of a tumor in an individualized treatment approach.

The median follow-up of the trial at the time point of analysis was 5. The design, patient evaluation, and end points of this trial have been published elsewhere.

Informed consent was obtained in accordance with the Declaration of Helsinki. Interphase fluorescence in situ hybridization analysis was performed on purified myeloma cells as previously described. Principle component analysis of the array data identified 2 outlier cases that were excluded from further analyses.

The expression values were Robust Multi-array Average normalized and log2-transformed using the statistical software package R. Cell line identities were confirmed for all cell lines by performing short tandem repeat profiling.

Associated Data

Gene-specific methylation was analyzed by bisulfite pyrosequencing and gene expression by reverse transcription-polymerase chain reaction RT-PCR. Details of pyrosequencing and primer sequences are provided in the supplemental Materials and methods.

Data processing and statistical analysis Methylation values were processed using GenomeStudio Illumina. K-means clustering and statistical analyses were performed in R 2.

The association with overall survival OS for low and high methylation groups was estimated for each methylation probe using the Kaplan-Meier methods log-rank test. The independence of the methylation groups from other established risk factors was tested by multivariate Cox regression analysis.

Results Categorization of DNA methylation data and survival analysis.Aberrant hypermethylation in the promoter regions of tumor suppressor genes is a crucial epigenetic alteration that involves the deregulation of many cellular processes that lead to the initiation and progression of human cancers.1–3 Several studies have suggested that methylation of multiple tumor suppressor genes in hepatocellular.

Methylation of tumor suppressor genes in ovarian cancer - Europe PMC Article - Europe PMC

The ME tumor-suppressor kit contains 26 probe sequences corresponding to a set of 24 tumor suppressor genes frequently silenced by methylation and 15 control probes that are not affected by methylation-sensitive HhaI restriction digestion. The researchers examined methylation levels of five tumor-suppressor genes.

Their findings indicate that methylation of RASSF1A and other genes increases steadily during the years of ovarian. DNA methylation is considered as a significant mechanism that silences tumor suppressor genes (TSGs) and could be used in the early diagnosis of cancer.

Histone modifications often work together with DNA methylation; however, how these epigenetic alterations regulate TSGs remains unclear. CONCLUSIONS: DNA methylation of tumor suppressor and metastasis suppressor genes is a hallmark of CTCs and confirms their heterogeneity.

Our findings add a new dimension to the molecular characterization of CTCs and may underlie the acquisition of . Altered methylation patterns of selected tumor suppressor genes and oncogenes have been associated with cancers in different populations, regardless of tumor type.

Studying these genes might provide a generalized insight into their role in altered cancer risk in a given population.

DNA methylation - Wikipedia