Methylation specific oligonucleotide microarray, also known as MSO microarray, was developed as a technique to map

epigenetic methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These te ...

changes in DNA of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

cells. The general process starts with modification of DNA with

bisulfite The bisulfite ion (IUPAC-recommended nomenclature: hydrogensulfite) is the ion . Salts containing the ion are also known as "sulfite lyes". Sodium bisulfite is used interchangeably with sodium metabisulfite (Na2S2O5). Sodium metabisulfite diss ...

, specifically to convert ''unmethylated'' cytosine in

CpG sites The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG isl ...

to uracil, while leaving ''methylated'' cytosines untouched. The modified DNA region of interest is amplified via

PCR PCR or pcr may refer to: Science * Phosphocreatine, a phosphorylated creatine molecule * Principal component regression, a statistical technique Medicine * Polymerase chain reaction ** COVID-19 testing, often performed using the polymerase chain r ...

and during the process, uracils are converted to thymine. The

amplicons In molecular biology, an amplicon is a piece of DNA or RNA that is the source and/or product of amplification or replication events. It can be formed artificially, using various methods including polymerase chain reactions (PCR) or ligase cha ...

are labelled with a

fluorescent dye A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with sev ...

and hybridized to oligonucleotide probes that are fixed to a glass slide. The probes differentially bind to cytosine and thymine residues, which ultimately allows discrimination between methylated and unmethylated CpG sites, respectively. A calibration curve is produced and compared with the microarray results of the amplified DNA samples. This allows a general quantification of the proportion of methylation present in the region of interest. This microarray technique was developed by Tim Hui-Ming Huang and his laboratory and was officially published in 2002. MSO microarray diagram

Implications for cancer research

Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

cells often develop atypical

methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...

patterns, at

in promoters of

tumour suppressor genes A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...

. High levels of methylation at a promoter leads to downregulation of the corresponding genes and is characteristic of

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

. It is one of the most consistent changes observed in early stage tumour cells. Methylation specific oligonucleotide microarray allows for the high resolution and high throughput detection of numerous methylation events on multiple gene promoters. Therefore, this technique can be used to detect aberrant methylation in tumour suppressor promoters at an early stage and has been used in gastric and colon cancers and multiple others. Because it allows one to detect presence of atypical methylations in cancer cells, it can also be used to reveal the major cause behind the malignancy, whether its main contributor is mutations on chromosomes or epigenetic modifications, as well as which tumour suppressor genes' transcription levels are affected. An interesting use of this microarray includes specific classification of cancers based on the methylation patterns alone, such as differentiating between classes of

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

, suggesting that different classes of cancer show relatively unique methylation patterns. This technique has also been proposed to monitor cancer treatments that involve modifying the methylation patterns in mutant cancer cells.

References

External links

Resources, information and specific protocols for DNA Methylation Analysis Software for DNA Methylation Analysis
Cancer research Microarrays {{oncology-stub