title: High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine.
abstract: Approximately 15 % of colorectal carcinomas (CRC) display high level microsatellite instability (MSI-H) due to either a germline mutation in one of the genes responsible for DNA mismatch repair (Lynch syndrome, 3 %) or somatic inactivation of the same pathway, most commonly through hypermethylation of the MLH1 gene (sporadic MSI-H, 12 %). Although heterogeneous, MSI-H colorectal carcinomas as a group show some distinct biologic characteristics when compared to CRC with stable or low level microsatellite instability. In the present review we will highlight therapeutically relevant characteristics of MSI-H tumors which could lead to specific responses to some conventional chemotherapy or novel targeted therapy agents.
authors.affiliation: Caris Life Sciences, 4610 South, 44th Place, Phoenix, AZ, 85040, USA. zgatalica@carisls.com.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.affiliation: Department of Pathology, University Clinical Center of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Semir
authors.initials: S
authors.lastname: Vranic
authors.affiliation: Caris Life Sciences, 4610 South, 44th Place, Phoenix, AZ, 85040, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Xiu
authors.affiliation: Caris Life Sciences, 4610 South, 44th Place, Phoenix, AZ, 85040, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Swensen
authors.affiliation: Caris Life Sciences, 4610 South, 44th Place, Phoenix, AZ, 85040, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Reddy
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D018095:Germ-Line Mutation; D006801:Humans; D053842:Microsatellite Instability; D058990:Molecular Targeted Therapy; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D057285:Precision Medicine; D011401:Promoter Regions, Genetic
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes
keywords: Biomarkers; Colorectal cancer; Conventional chemotherapy; Lynch syndrome; Microsatellite instability; Targeted therapy