Pancreatic cancer is one of the most lethal malignancies and somatic mutations of protocadherins have been identified. Some of them are recently identified as tumor-suppressor genes, in particular PCDH10 is a functional TSG frequently silenced by methylation in multiple carcinomas. Our goal is to evaluate the prognostic significance of protocadherins methylation in pancreatic adenocarcinoma so we studied methylation in primary pancreatic cancers. Functional assays with a PCDH10 re-expressing pancreatic cancer cell line is in progress to characterize its biological effects in pancreatic tumorigenicity. Material and methods. 38 ductal pancreatic adenocarcinomas were recruited in “Casa sollievo della sofferenza” Hospital, S.Giovanni Rotondo. DNA was extracted from tumor tissue and treated with bisulfite solution. Then COBRA analysis and bisulfite genomic sequencing were used to determine the presence of methylated CpG in the promoters region. A functional assay using AspC-1 and Capan-2 pancreatic cancer cell lines trasfected with the full length PCDH10 will assess the effect of PCDH10 on pancreatic cancer cell growth. Results. Cases were studied for PCDHAC2, PCDHGC5 and PCDH10 methylation status and IHC. Results showed no PCDHAC2 methylation pattern and a ubiquitously methylation of PCDHGC5 in all cases analysed. PCDH10 analysis showed a partial methylation pattern in 9/18 and no methylation in 9/18 cases analysed. IHC analysis detected PCDHAC2 expression in 6% of cases analysed and PCDHGC5 in 30%. IHC of PCDH10 is in progress. Conclusion. The identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic, and therapeutic applications. PCDH10 may be a potential target gene for cancer gene theraphy.
Methylation analysis of protocadherin genes in pancreatic adenocarcinoma
CURIA, Maria Cristina;FANTINI, FABIANA;LATTANZIO, ROSSANO;DI MARCANTONIO, Maria Carmela;SAVINO, LUCA;PIANTELLI, Mauro;BATTISTA, Pasquale;Di Sebastiano, Pierluigi;CAMA, Alessandro
2016-01-01
Abstract
Pancreatic cancer is one of the most lethal malignancies and somatic mutations of protocadherins have been identified. Some of them are recently identified as tumor-suppressor genes, in particular PCDH10 is a functional TSG frequently silenced by methylation in multiple carcinomas. Our goal is to evaluate the prognostic significance of protocadherins methylation in pancreatic adenocarcinoma so we studied methylation in primary pancreatic cancers. Functional assays with a PCDH10 re-expressing pancreatic cancer cell line is in progress to characterize its biological effects in pancreatic tumorigenicity. Material and methods. 38 ductal pancreatic adenocarcinomas were recruited in “Casa sollievo della sofferenza” Hospital, S.Giovanni Rotondo. DNA was extracted from tumor tissue and treated with bisulfite solution. Then COBRA analysis and bisulfite genomic sequencing were used to determine the presence of methylated CpG in the promoters region. A functional assay using AspC-1 and Capan-2 pancreatic cancer cell lines trasfected with the full length PCDH10 will assess the effect of PCDH10 on pancreatic cancer cell growth. Results. Cases were studied for PCDHAC2, PCDHGC5 and PCDH10 methylation status and IHC. Results showed no PCDHAC2 methylation pattern and a ubiquitously methylation of PCDHGC5 in all cases analysed. PCDH10 analysis showed a partial methylation pattern in 9/18 and no methylation in 9/18 cases analysed. IHC analysis detected PCDHAC2 expression in 6% of cases analysed and PCDHGC5 in 30%. IHC of PCDH10 is in progress. Conclusion. The identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic, and therapeutic applications. PCDH10 may be a potential target gene for cancer gene theraphy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
