Methylation of adenomatous polyposis coli (APC) gene promoter is a generalized feature on molecular pathology tests of sporadic renal cell carcinomas in Taiwan

Abstract Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Approximately 50% to 80% of sporadic RCCs are associated with mutations in the von Hippel-Lindau (VHL) gene in Western countries. The aim of this study is to elucidate the possible etiological role of molecular pathogenesis in sporadic RCCs in Taiwan.Methods: Fifteen patients with RCC were screened for mutations in the VHL gene and methylation statuses of promoters of 24 tumor suppressor genes. Mutations were identified by PCR and Sanger sequencing. Methylation statuses were determined on methylation sensitive multiplex ligation-dependent probe amplification (MS-MLPA) analysis.Results: Inactivation of VHL gene was observed in 5 cases: three missense somatic mutations, V155G in case 1, N141S in case 5, and E52D in case 9; promoter methylation in case 3; and small deletion in case 13. RCCs were most frequently methylated at APC (100%, 14/14), CDKN2B (92.9%, 13/14), CASP8, MLH1_167, and KLLN (85.7.4%, 12/14), but not at FHIT, MLH1_463, DAPK1, or HIC1 (0%).Conclusions: In addition to VHL inactivation, promoter methylation of APC and CDKN2B may play important roles in the tumorigenesis of RCC. Methylation of APC may be a very early pathognomonic event in tumorigenesis of RCC and a candidate diagnostic and therapeutic biomarker.