Proximal Short Tandem Repeat Variations as Regulators of Gene Expression across Multiple Cancers
Feifei Xia (ZHAW)

Zurich Seminars in Bioinformatics

  • 12:15 UZH Irchel Y55-l-06/08 and ZOOM Call

Abstract Short tandem repeats (STRs) have been reported as potential regulators of gene expression changes in healthy populations and colorectal cancer (CRC). While STR mutations are also enriched in stomach cancer (STAD) and endometrial cancer (UCEC), especially in tumors with the microsatellite instability (MSI) phenotype, the functional impacts of STRs on gene expression remain unclear across cancer types. In particular, previous studies were mostly limited to association analyses between single STR locus and gene expression.

Using whole exome sequencing, gene expression, and clinical information from TCGA, we examined the linear relationships between gene expression and STR length variations in the gene region. We identified 714, 359, and 101 expression STRs (eSTRs) in CRC, STAD, and UCEC, respectively, of which 10 genes are shared in all three cancer types. We then extended our analysis by performing conditional analyses to discover the eSTRs showing independent functional effects within the context of MSI phenotype. Moreover, we found that the lengths of eSTRs proximal to a gene are often correlated with each other and have consistent effects on the expression levels of the gene. Our findings can expand the catalog of genetic variants that affect gene expression, underlying the importance of STR variants in tumorigenesis and suggesting coordinated potential regulatory mechanisms across diverse cancer types.