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Background   ADAMTS19  encodes a member of the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) protein family with emerging roles in carcinogenesis and metastasis. ADAMTS shares several distinct protein modules including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. In a previous work, we found  ADAMTS19  frequently hypermethylated in colorectal cancer (CRC). We explored the association of methylation with tumor genotype and phenotype.    Results  The methylation status of the CpG island in the promoter of  ADAMTS19  was determined in 252 colorectal, 65 pancreatic, 33 breast and 169 ovarian primary tumors, 70 CRC metastases, and 10 CRC cell lines. Tumor-specific methylation of  ADAMTS19  was significantly more frequent in gastrointestinal than in gynecological cancers (odds ratio (OR) = 2.9, confidence interval (CI) = (1.9–4.7),  p =  5.2 × 10 −7 ) and was independent of the methylation of adjacent  loci  in CRC. Hypermethylation associated with CRC with mutated  BRAF  oncogene (OR = 10.1, CI = (3.1–42.9),  p =  6.3 × 10 −6 ) and with the mucinous phenotype in CRC (OR = 2.1, CI = (1.1–4.1),  p =  0.023) and ovarian cancer (OR = 60, CI = (16–346),  p =  4 × 10 −16 ). Methylation was significantly more frequent in CRC metastases homing to the ovary and omentum than in those homing to the liver and lung (OR = 6.1, CI = (1.8–22.2),  p =  0.001). Differentiating local from distant metastatic spread, methylation negatively associated with tumor progression ( p  = 0.031) but positively with depth of invasion ( p  = 0.030). Hypermethylation associated with transcriptional repression in CRC cell lines, and treatment with 5′-AZA-2′-deoxycytidine led to reactivation of mRNA expression. shRNA-mediated silencing of  ADAMTS19  had no effect on the in vitro proliferation rate of CRC cells but significantly diminished their collective migration speed (56 %,  p =  3.3 × 10 −4 ) and potential to migrate in collagen I (64 %,  p =  4.3 × 10 −10 ).    Conclusions  Our results highlight the frequent involvement of  ADAMTS19  epigenetic silencing in CRC and mucinous ovarian cancer. The mechanistic preferences for the target organ of metastatic spread may lead to the development of diagnostic CRC biomarkers. The association with the mucinous phenotype also may have diagnostic applications for ovarian cancer.    Electronic supplementary material  The online version of this article (doi:10.1186/s13148-015-0158-1) contains supplementary material, which is available to authorized users.

Epigenetic inactivation of the extracellular matrix metallopeptidase ADAMTS19 gene and the metastatic spread in colorectal cancer