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Multi-omics Analysis
Published in Altuna Akalin, Computational Genomics with R, 2020
Another way to ascribe biological significance to the latent variables is by correlating them with additional covariates we might have about the samples. In our example, the colorectal cancer tumors have also been characterized for microsatellite instability (MSI) status, using an external test (typically PCR-based). By examining the latent variable values as they relate to a tumor’s MSI status, we might discover that we’ve learned latent factors that are related to it. The following code snippet demonstrates how this might be looked into, by generating Figures 11.16 and 11.17:
Colorectal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Genetic instability at the DNA level, which includes MSI and Lynch syndrome, occurs as a result of DNA replication errors. Mutations with functional effects in any of the complex genomic replication, detection, and repair systems that are responsible for ensuring that replicated DNA is of perfect fidelity can lead to DNA errors and eventually, a hypermutated genome. MSI (also known as mismatch repair-deficient [dMMR]) is found in 15–20% of primary colonic cancers, but in metastatic disease, it is less common at around 4%, as MSI tumors relapse less frequently. Microsatellites are sections of DNA in which a short sequence of DNA is repeated multiple times. MSI is classified when a microsatellite has gained or lost repeat units and has undergone a change in length, which results in frame-shift mutations or base-pair mutations, or both. It is typically associated with DNA mismatch repair defects, in particular mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Studies exploring the correlation of MSI with response to chemotherapy in MCRC are controversial but increasingly suggest no, or poor, response to conventional cytotoxic chemotherapy. In the adjuvant Dukes’ B setting, chemotherapy confers no benefit; MSI is both prognostic and predictive of non-response and a favorable prognostic factor and should be tested routinely.157,158
Bladder cancer: superficial
Published in J Kellogg Parsons, E James Wright, The Brady Urology Manual, 2019
Microsatellite analysis: Detects expansion, deletion, and loss of heterozygosity in repetitive DNA sequencesFalse-positive results may occur with cystitis and benign prostatic hyperplasia (BPH).16
What role does adjuvant therapy play in the management of endometrial cancer?
Published in Expert Opinion on Pharmacotherapy, 2023
Gloria Shining Huang, Joan Tymon-Rosario, Alessandro D. Santin
Cancer cells with a high number of mutations within microsatellites (short, repeated sequences of DNA) can be categorized as microsatellite instability-high (MSI-H) if 30% or more microsatellite loci show mutations. The MSI-H DNA signature reflects impaired ability to correct mistakes that occur during DNA replication. Microsatellite instability is found most often in colorectal cancer, gastric cancer, and endometrial cancer. MSI-H endometrial tumors originate from different molecular pathways including germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2), somatically acquired MMR gene mutations, or methylation of the MLH1 gene promoter; these genomic alterations result in loss of expression or function of the MMR protein. It is estimated that 20% of the endometrial cancers harbor such mismatch repair defects.
Targeting NKG2A to boost anti-tumor CD8 T-cell responses in human colorectal cancer
Published in OncoImmunology, 2022
Kathleen Ducoin, Romain Oger, Linda Bilonda Mutala, Cécile Deleine, Nicolas Jouand, Juliette Desfrançois, Juliette Podevin, Emilie Duchalais, Jonathan Cruard, Houssem Benlalam, Nathalie Labarrière, Céline Bossard, Anne Jarry, Nadine Gervois-Segain
Microsatellite instability or mismatch repair status was performed for diagnosis purposes by PCR or immunohistochemistry studies, respectively, as previously described.16 Microsatellite instability status was determined using pentaplex PCR with five markers: BAT-25, BAT-26, NR-21, NR-22, NR-24.20 Briefly, genomic DNA was extracted from 10 µm thick tissue sections of formalin-fixed, paraffin-embedded colorectal tumor tissues after manual macrodissection using the iPrepTM ChargeSwitch® Forensic kit (Invitrogen), and according to the manufacturer’s instructions. A colorectal tumor was considered as microsatellite instable if at least two of these five markers showed microsatellite instability.21 Mismatch repair status was assessed by immunohistochemistry using the following mAbs: MLH1 (Agilent Technologies, ES05, RRID:AB_2877720), MSH2 (Agilent Technologies, FE11, RRID:AB_2889974), MSH6 (Agilent Technologies, EP49, RRID:AB_2889975) and PMS2 (Agilent Technologies, EP51, RRID:AB_2889977).
Combining inhibition of immune checkpoints and PARP: rationale and perspectives in cancer treatment
Published in Expert Opinion on Therapeutic Targets, 2022
Martina Catalano, Luigi Francesco Iannone, Federica Cosso, Daniele Generali, Enrico Mini, Giandomenico Roviello
Microsatellites are distributed throughout the human genome, arranged in tandem and particularly prone to accumulate errors during the DNA replication. The state of microsatellite instability can be defined through two main methods: molecular tests of MSI analysis carried out on DNA extracted from neoplastic cells and evaluation of the immunohistochemical expression of the proteins of the MMR system on neoplastic tissue sections. Among the most used panels for MSI detection, Pentaplex analyzes 5 loci and defines MSI when at least three loci are unstable, whereas tumors with none or an unstable locus are considered microsatellite stable (MSS). Using larger panels, the tumor is considered MSS when no locus (0%) results unstable, MSI-low with unstable loci less than 30% and MSI-high if greater than 30% [12].