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Background  Colorectal cancer (CRC) is closely linked to Wnt signalling, with 94 % of cases exhibiting a Wnt related mutation. ROR2 is a receptor tyrosine kinase that is thought to repress β-catenin dependent Wnt signalling. Our study aims to determine if  ROR2  is epigenetically silenced in CRC and determine if in vitro silencing of  ROR2  potentiates Wnt signalling, and alters the proliferative, migratory or invasive potential of cells.    Methods   ROR2  expression was examined in CRC cell lines and patient adenomas using qRT-PCR, while COBRA and bisulphite sequencing was used to analyse  ROR2  promoter methylation. 258 patient primary tumour samples from publicly available databases were also examined for  ROR2  expression and methylation. In addition, the functional effects of  ROR2  modulation were investigated in HCT116 cells following  ROR2  siRNA knockdown and in RKO and SW620 cells following ectopic  ROR2  expression.    Results  Reduced  ROR2  expression was found to correlate with  ROR2  promoter hypermethylation in colorectal cancer cell lines, carcinomas and adenomas.  ROR2  expression was downregulated in 76.7 % (23/30) of CRC cell lines with increasing  ROR2  promoter hypermethylation correlating with progressively lower expression. Analysis of 239 primary tumour samples from a publicly available cohort also found a significant correlation between reduced  ROR2  expression and increased promoter methylation. Methylation analysis of 88 adenomas and 47 normal mucosa samples found greater percentage of adenoma samples to be methylated. Additional analysis also revealed that adenoma samples with reduced  ROR2  expression also possessed  ROR2  promoter hypermethylation.  ROR2  knockdown in the CRC cell line HCT116 significantly decreased expression of the β-catenin independent Wnt targets genes  JNK  and  NFATC1 , increased cellular proliferation and migration but decreased invasion. When  ROR2  was ectopically expressed in RKO and SW620 cells, there was no significant change to either cellular proliferation or migration.    Conclusion   ROR2  is frequently epigenetically inactivated by promoter hypermethylation in the early stages of colorectal neoplasia and this may contribute to colorectal cancer progression by increasing cellular proliferation and migration.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-016-2576-7) contains supplementary material, which is available to authorized users.

ROR2 is epigenetically inactivated in the early stages of colorectal neoplasia and is associated with proliferation and migration