Latest Development of Microsatellite Instability in Cancer

A special issue of Current Oncology (ISSN 1718-7729).

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 594

Special Issue Editor


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Guest Editor
Institute for Population and Precision Health, University of Chicago, Chicago, IL 60637, USA
Interests: integrative molecular genomics in cancer epidemiology; oncogenesis and its use in disease classification; therapeutic response and prognosis of different human cancers

Special Issue Information

Dear Colleagues,

Microsatellites are short, repeated sequences of DNA. Microsatellite instability (MSI) refers to a change that occurs in certain cells (such as cancer cells) in which the number of repeated DNA bases in a microsatellite is different from what it was when the microsatellite was inherited. Microsatellites make up approximately three percent of the human genome. Microsatellites are seen twice as much at the ends of chromosome arms than in the chromosome bodies. The majority of repeats occur in untranslated regions, specifically introns. However, microsatellites that occur in coding regions often inhibit the expansion of most downstream events. MSI may be caused by slipped strand mispairing or mistakes that don’t get corrected by mismatch repair (MMR) when DNA is copied in a cell. Some studies show an association between MSI and tumor DNA methylation in cancer. MSI is found most often in colorectal cancer, however it has been seen in other types of cancer including gastric, liver, pancreatic, endometrial, ovarian, prostate cancer as well as other cancers.

From the diagnostic point of view, the detection of the MSI pathology includes (a) single-plex and multiplex PCR (typically reported as MSI-high/MSI-low), (b) immunohistochemistry (typically reported as deficient MMR or dMMR) and (c) next-generation sequencing. Also, to note that different markers may be detected or reported in different tumors. There is also an interest in detection of MSI is liquid biopsy samples.

MSI has prognostic implication. In general MSI, in early stage colorectal cancer, shows good prognosis; however in advanced colorectal carcinoma or in breast cancer the presence of MSI may show poor prognosis.

From the therapeutic point of view, MSI has significant clinical implication especially for immune check-point inhibitors (ICI).  It is possible that dMMR cancer cells may produce heterologous antigens and therefore those cancer cells may be easily recognized by host T-cells. There is evidence that the effectiveness of PD-1 inhibitors on solid tumors with MSI is higher than that of MSS solid tumors. MSI may be a proxy for overexpression of some immune target genes (including PD-1, CTLA4 and HAVCR2) in the cancer tissue, which are targeted by the different ICIs.

Considering these facts, in this special issue, we would like to invite original and review papers addressing (a) basic and molecular pathology of MSI in human cancer, (b) development and/or improvement of cost-effective MSI detection assay technology and/or NGS algorithm and (c) clinical translational application of MSI in cancer therapeutics.

You may choose our Joint Special Issue in Cancers.

Dr. Muhammad Kibriya
Guest Editor

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Keywords

  • microsatellite instability

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