HITTING the MARK in CANCER EPIGENETICS Research in Cancer Epigenetics Is Advancing Rapidly

HITTING THE MARK IN CANCER EPIGENETICS Research in cancer epigenetics is advancing rapidly. Here’s an overview of the tools and methods scientists use to drive progress in the field. For by CUSTOM MEDIA ADVERTISEMENT FEATURE ADVERTISEMENT FEATURE says. “We usually put these cytosine ring — is the best look and behave. Illumina’s Andrew Feber, a cancer patients on a watch and understood epigenetic marker methylation array covers geneticist at UCL Cancer HITTING THE MARK wait scheme. We could have today. Methylation typically 850,000 sites on the Institute in London, is one spared her all that therapy.” silences gene transcription genome, and analyses with of those scientists. He aims Pfister’s experience in patterns that are it, he says, “are sufficient to find epigenetic traces IN CANCER EPIGENETICS illustrates the growing characteristic to specific cell to capture the cancer cell’s of bladder cancer in urine, potential of genomic types and tissues. But when basic identity”. an endeavour he says is RESEARCH IN CANCER EPIGENETICS IS ADVANCING RAPIDLY. Here’s an overview of the tools technologies in epigenetics to it silences tumour suppressor Esteller points out that particularly well suited to and methods scientists use to drive progress in the field. contribute to understanding, genes, cancer may appear. methylation arrays have sequencing since it can diagnosing and treating The first epigenetic many positive aspects, such read the often fragmented cancer. Epigenetic technologies — methylation as low-cost and amenability arrangements of DNA modifications to DNA and arrays — emerged about 15 to formalin-fixed, paraffin- letters in liquid specimens. n 2013 Stefan Pfister, RNA regulate how and when years ago with the launch embedded tissue samples. “We can use it to identify a paediatric neuro- genes are turned on or off, of the National Cancer In his own research, he has patients with bladder I oncologist at Heidelberg and they play crucial roles in Institute’s Cancer Genome used arrays to identify which cancer earlier, and also to University Hospital, had to normal cell differentiation. Atlas project. These tools patients with non-small-cell interrogate aspects such as deliver devastating news to When epigenetic processes are designed to probe lung cancer will probably inter-tumour heterogeneity the family of a 12-year-old girl. heavily methylated regions benefit most from anti-PD-1 and subclonal epigenetic WATCHARA/SHUTTERSTOCK She had been diagnosed with on DNA, including CpG immunotherapy, and to find alterations that occur glioblastoma, a fast-growing “IF WE HAD islands dominated by the out where metastatic cancers in only a fraction of the and potentially lethal brain KNOWN SHE presence of cytosine-guanine of unknown primary origins tumour cells in a sample,” cancer. Even though she HAD A GLIOMA, sequences. (see ‘How to (CUP) come from. he explains. would receive radiation and WE WOULDN’T decode epigenetic factors’). Among the various chemotherapy, Pfister did HAVE TOLD HER And they’re still workhorses Sequencing Moves approaches, bisulfite not expect her to live more FAMILY THAT in the field. to the Fore sequencing is the most than 18 months. But he was SHE HAD LITTLE Using an array that covers Methylation arrays, widely adopted. The wrong. Three years after her CHANCE OF 450,000 genomic sites to however, only interrogate process involves treating treatments, the young girl A CURE.” scan tumour samples from limited regions of DNA a DNA sample with was thriving. just over 2,800 patients, for target alterations. sodium bisulphate, which Pfister, who also directs are dysregulated, however, Pfister and his colleagues has the effect of making the German Cancer these modifications can achieved a major advance methylated cytosines more Research Center on the cause gene expression to go in the diagnosis of central “WE SEE visible. That’s because hospital campus, was awry and potentially spawn nervous system (CNS) APPLICATIONS the chemical treatment able to determine why. A tumours. Tools such as cancers. Published in 2018, FOR SEQUENCING converts unmethylated genomic scan of the girl’s genomic arrays and next- the research revealed 82 ACROSS THE cytosines on DNA to tumour revealed epigenetic generation sequencing can distinct tumour classes, only BOARD IN uracil, while leaving the methylation patterns reveal previously unseen some of which were already EPIGENETICS.” methylated forms of cytosine consistent with low-grade epigenetic marks such as known1. Freely available — 5-methylcytosine and glioma, which is slow-growing DNA methylation, histone online, and now used in Epigenetic sequencing, on 5-hydroxymethylcytosine — and curable, and hard to modifications and chromatin more than 10 countries, the other hand, provides an unchanged. Using specialized distinguish from glioblastoma remodelling, allowing “the new classifier allows opportunity to study much software, scientist can on the basis of histology. The scientists to “gain a better for standardized tumour larger swaths of the cancer then map out where the memory of that diagnostic understanding of cancer and diagnostics informed by epigenome — including methylated bases are, and error sticks with him. “If how it evolves”, says Manel DNA methylation patterns how regulatory elements in hunt for epigenetic variants we had known she had a Esteller, director of Josep distinguishing the different tumorigenesis evolve. And as indicative of cancer. Feber glioma, we wouldn’t have Carreras Leukaemia Research brain tumour entities”, Pfister costs fall steadily, epigenetic and his colleagues relied told her family that she had Institute (IJC), in Barcelona. In says. These patterns are sequencing is making steady on the bisulfite method to little chance of a cure,” he turn, these insights will lead to reflective of the cell type inroads in cancer research. find epigenetic markers for new opportunities in diagnosis that each of the different “We see applications for bladder cancer that have and treatment. tumours emerged from, as sequencing across the board since been incorporated well as their differentiation in epigenetics,” says Phillip into a diagnostic test being Epigenetic marks are what Methylation Arrays states when the malignant Febbo, Illumina’s chief evaluated in a clinical trial allow the same DNA in each cell DNA methylation — the transformations occurred. medical officer. “The lion’s with more than 16,000 to be transcribed into different process by which methyl or According to Pfister, this share of scientists who look at patients2. proteins across the body. Disrupted epigenetic processes hydroxymethyl groups attach cellular context predicts methylation patterns are now This test could provide a can contribute to cancer. to the C5 position on the how a tumour is likely to switching to these methods.” non-invasive alternative to Advertiser retains sole responsibility for content Advertiser retains sole responsibility for content ADVERTISEMENT FEATURE ADVERTISEMENT FEATURE cystoscopy, which poses an HOW TO DECODE EPIGENETIC FACTORS Meanwhile, scientists scientists are now and their influence on biologist who studies infection risk. The test was can also obtain combining ChiP-seq with cancer processes. He uses cancer epigenetics at developed with targeted DNA can be modified in several different ways that alter gene expression. complementary epigenetic a specific chromosome it to study varied chromatin Jackson Laboratories in bisulfite sequencing, Here are four of the common technologies that researchers are using to probe information by combining conformation capture states in bladder cancer Farmington, Connecticut, the epigenetic modifications. which zeroes in on specific sequencing with other technique known as epithelial cells. And in a says single cell genomic regions. However, approaches. One of them, HI-C, which allows for 2018 study, researchers applications will advance scientists can also use known as ChIP-seq, reveals high-throughput, high her own efforts at finding whole genome bisulfite how proteins interact resolution analyses epigenetic biomarkers 1 Methylation arrays sequencing to discover with different sites on of the interaction of “AFTER WE BREAK in blood that predict These identify a curated subset of methylated entirely new epigenetic the genome. Performed regulatory elements and how patients respond to cytosine bases. Cancer progression is linked 2 Bisulﬁte sequencing THAT COST 6 pathways in cancer. Though with DNA methylation: hypermethylation Treating DNA with sodium bisulphate by combining chromatin their target genes . “We BARRIER, WE’LL specific treatments for it’s currently expensive inactivates tumour-suppressor genes whereas causes only the unmethylated cytosines immunoprecipitation come at epigenetics ROUTINELY BE leukemia. When it comes and difficult to perform, hypomethylation activates oncogenes. to convert to uracil. Sequencing then (ChIP) with parallel from the standpoint ABLE TO LOOK to single-cell research, whole genome bisulfite reveals where the methylated cytosines sequencing, ChIP-seq of transcriptional AT THE TUMOUR there’s still a cost barrier sequencing amounts to remain in the genome. identifies binding sites regulation and chromatin EPIGENOME WITH to contend with. “After the most comprehensive for transcription factors, modification, and how SINGLE-CELL we break that cost approach for discovering Silenced gene and provides additional they change with cancer RESOLUTION.” barrier, we’ll routinely be Me Me new epigenetic

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