MSIMEP: Predicting microsatellite instability from microarray DNA methylation tumor profiles

Martín Santamarina-García, Jenifer Brea-Iglesias, Jesper Bertram Bramsen, Mar Fuentes-Losada, Francisco Javier Caneiro-Gómez, José Ángel Vázquez-Bueno, Héctor Lázare-Iglesias, Natalia Fernández-Díaz, Laura Sánchez-Rivadulla, Yoel Z. Betancor, Miriam Ferreiro-Pantín, Pablo Conesa-Zamora, José Ramón Antúnez-López, Masahito Kawazu, Manel Esteller, Claus Lindbjerg Andersen, Jose M.C. Tubio, Rafael López-López*, Juan Ruiz-Bañobre

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review


Deficiency in DNA MMR activity results in tumors with a hypermutator phenotype, termed microsatellite instability (MSI). Beyond its utility in Lynch syndrome screening algorithms, today MSI has gained importance as predictive biomarker for various anti-PD-1 therapies across many different tumor types. Over the past years, many computational methods have emerged to infer MSI using either DNA- or RNA-based approaches. Considering this together with the fact that MSI-high tumors frequently exhibit a hypermethylated phenotype, herein we developed and validated MSIMEP, a computational tool for predicting MSI status from microarray DNA methylation tumor profiles of colorectal cancer samples. We demonstrated that MSIMEP optimized and reduced models have high performance in predicting MSI in different colorectal cancer cohorts. Moreover, we tested its consistency in other tumor types with high prevalence of MSI such as gastric and endometrial cancers. Finally, we demonstrated better performance of both MSIMEP models vis-à-vis a MLH1 promoter methylation-based one in colorectal cancer.

Antal sider16
StatusUdgivet - mar. 2023


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