RT Journal Article SR Electronic T1 Short tandem repeat mutations regulate gene expression in colorectal cancer JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.11.29.569189 DO 10.1101/2023.11.29.569189 A1 Verbiest, Max A. A1 Lundström, Oxana A1 Xia, Feifei A1 Baudis, Michael A1 Sonay, Tugce Bilgin A1 Anisimova, Maria YR 2023 UL http://biorxiv.org/content/early/2023/11/29/2023.11.29.569189.abstract AB Short tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations in CRC remains unclear. Here, we integrate STR mutation data with clinical information and gene expression levels to study the gene regulatory effects of STR mutations in CRC. We confirm that STR mutability in CRC highly depends on the MSI status, repeat unit size, and repeat length. Furthermore, we present a set of 1244 putative expression STRs (eSTRs) for which the STR length is associated with gene expression levels in CRC tumours. The length of 73 eSTRs is associated with expression levels of cancer-related genes, nine of which are CRC-specific genes. We show that linear models describing eSTR-gene expression relationships allow for predictions of gene expression changes in response to eSTR mutations. Moreover, we found an increased mutability of eSTRs in MSI tumours. Our evidence of gene regulatory roles for eSTRs in CRC highlights a mostly overlooked way through which tumours may modulate their phenotypes. The increased mutability of eSTRs in MSI tumours may be an early indication that eSTR mutations can confer a selective advantage to tumours. Future extensions of our findings into larger cohorts could uncover new STR-based targets in the treatment of cancer.Competing Interest StatementThe authors have declared no competing interest.