36 results about "Epigenetic Change" patented technology

Methods are provided for the identification of compounds that selectively modulate epigenetic changes in gene expression. Compounds, compositions, kits or assays devices, and methods are provided for modulating the expression, endogenous levels or the function of small non-coding RNAs cognate to or transcribed by heterochromatic regions subject to epigenetic regulation (i.e., promoters, enhancers, centromeres, telomeres, origins of DNA replication, imprinted loci, or loci marked by dosage-compensation), and for modulating the formation or function of heterochromatin in cells, tissues or animals.

We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island hypermethylation and transcriptional silencing in colorectal cancer (CRC). By screening cell lines andvalidating tumor specific hypermethylation in a panel of primary human CRC samples, we estimate that nearly 5% of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find a much larger number of genes hypermethylated in individual tumors, and much higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. The genes we identified can be used inter alia diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.

We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island hypermethylation and transcriptional silencing in colorectal cancer (CRC). By screening cell lines and validating tumor specific hypermethylation in a panel of primary human CRC samples, we estimate that nearly 5% of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find a much larger number of genes hypermethylated in individual tumors, and much higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. The genes we identified can be used inter alia diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.

The present invention relates to a method of monitoring epigenetic changes comprising monitoring changes in conditional long range chromosomal interactions at at least one chromosomal locus where the spectrum of long range interaction is associated with a specific physiological condition, the method comprising the steps of:- (i) in vitro crosslinking of said long range chromosomal interactions present at the at least one chromosomal locus; (ii) isolating the cross linked DNA from said chromosomal locus; (iii) subjecting said cross linked DNA to restriction digestion with an enzyme that cuts at least once within the at least one chromosomal locus; (iv) ligating said cross linked cleaved DNA ends to form DNA loops; (v) identifying the presence of said DNA loops; wherein the presence of DNA loops indicates the presence of a specific long range chromosomal interaction.

Nucleic acid is an important genetic substance of a human body and plays an important role in storing, copying and transmitting genetic information, methylated DNA is one of main epigenetic modification modes, abnormal DNA sequences, base mutation and epigenetic changes often cause cancers, and in order to realize early target detection, the invention designs a tetrahedron-assisted multi-series hairpin cascade assembly detection target (DNA / RNA / methylated DNA and the like) universal electrochemical sensor, a plurality of hairpin cascade assemblies are incubated to trigger signal amplification reaction, electric signal detection is realized in a RuHex solution, and powerful electrostatic attraction acts on a DNA phosphoric acid skeleton to cause increase of DPV current response. The linear concentration range of target detection is 10 aM to 100 pM, and the lowest detection limit is 1.78 aM. By means of a specific enzyme digestion reaction, methylated DNA is incubated on an electrochemical platform to carry out related experiments, and the superiority of the platform is further proved.

Disclosed are methods of detecting a predisposition to, or the incidence of, bladder cancer in a sample comprising detecting an epigenetic change, such as methylation, in at least one gene selected from TWIST1, NID2, RUNX3, BMP7, CCNA1, PDLIM4, TNFRSF25, APC, RASSF1A, LOXL1, TUBB4, NTRK2, ARFGAP3, OSMR and TJP2, or a panel thereof. Also disclosed are kits for performing the disclosed methods, such as kits for detecting a predisposition to, or the incidence of, bladder cancer in a sample comprising at least one primer pair for determining the methylation status of each of NID2, TWIST1 and RUNX3. The kits may contain means for processing a urine sample.

The invention is directed to methods for angiotyping individual patients to predict the likelihood of whether a given individual will develop good vs. poor collaterals naturally. Accordingly, this can involve obtaining and providing a list of genes involved in collateral development. In particular, angiotyping individual patients can be used to predict the likelihood of whether a given individual will develop good vs. poor collaterals in response to specific angiogenesis therapy. From an array of genes that have been determined through experimental studies as being differentially expressed in tissues in which collaterals are developing in response to arterial occlusion, single nucleotide polymorphisms (SNPs), or other epigenetic changes, such as DNA methylation patterns, can be identified. SNPs and DNA methylation patterns are detected using microchips or similar technology assaying for all, or most, of the genes determined to play a role in collateral development. In addition, abnormally low or abnormally high differential expression of any combination of the candidate genes can be detected in such tissue as peripheral blood cells. The presence of a predisposition to develop poor vs. good collaterals is indicated by the presence of SNPs, and / or alterations in DNA methylation patterns, and / or difference in expression levels involving one or more of the genes.

It is proposed that cancer cells express SATB1, and that SATB1 acts as a determinant for the acquisition of metastatic activity by controlling expression of a specific set of genes that promote metastatic activity. In order for cancer cells to gain the ability to metastasize, SATB1 re-organizes or re-packages genomic sequences in a specific manner to allow a switch in the pattern of gene expression. SATB1 expression was found restricted mainly to aggressive cancer cells where it may regulate the genetic and epigenetic changes that program the steps involved in the metastatic process. The present invention describes reagents and tools to detect the SATB1 protein for use in diagnosis and prognosis of aggressive cancers and therapeutics to inhibit SATB1 protein to deplete its expression in metastatic and aggressive cancers.

The present invention is related to methods and compositions useful in the detection and treatment of epigenetic changes during traumatic, autoimmune and other disease processes. The methods described herein comprise identifying and using certain agents to modulate pathophysiological processes in animal and human subjects. The methods of the invention may be used for therapeutic or diagnostic purposes.

The present invention relates to methods for predicting the efficacy of anthracycline-based neo-adjuvant chemotherapy in triple-negative breast cancer. This is achieved by determining epigenetic changes within the PITX2 gene. Detection of the methylation state of Cp G sites in a genomic sequence of PITX2 allows an estimate of the response or failure of an individual breast cancer patient to neo-adjuvant therapy.

Assays using binding studies involving function of BRCA1a protein have use for diagnosis and for evaluation of possible tumorogenicity of agents, particularly estrogenic agents. The assays do not rely on use of a probe for only specific sequences, but on effects of known and unknown or not previously studied sequences (consequence of genetic changes) or posttranslational modification of BRCA1 proteins (as a consequence of epigenetic changes) as seen in hereditary and sporadic cancers.

A method of detecting a predisposition to, or the incidence of, bladder cancer in a sample comprises detecting an epigenetic change in at least one gene selected from FOXE1 and GATA4. Detection of the epigenetic change is indicative of a predisposition to, or the incidence of, bladder cancer. The sample comprises nucleic acid molecules from bladder cells. The methods may be used to select treatments and patients for treatment. Related kits include primers allowing the methylation status of the genes to be determined.

Disclosed are methods for assessing the methylation and mutation status of nucleic acid in a sample. The methods provide for methylation-dependent modification of the nucleic acid in a sample, and subsequently nucleic acid amplification processes to distinguish between mutated and non-mutated target sequence.

The invention relates to compounds and methods useful in detection and therapy of HPV-associated diseases. The invention is based on the elucidation of a mechanism by which replication of HPVs occurs in naturally infected tissues and cells. Moreover it is based on the identification of distinct epigenetic changes of the viral genome in infected cells that allows promotion of the affected cells to precancerous and cancerous cells. The invention therefore provides methods of diagnosing neoplasias and their precursor lesions as well as methods of preventing the development of malignancies or inhibiting tumor growth.