Journal article

Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic carcinoma


Authors listDammann, R; Schagdarsurengin, U; Liu, LM; Otto, N; Gimm, O; Dralle, H; Boehm, B; Pfeifer, GP; Hoang-Vu, C

Publication year2003

Pages3806-3812

JournalOncogene

Volume number22

Issue number24

ISSN0950-9232

eISSN1476-5594

DOI Linkhttps://doi.org/10.1038/sj.onc.1206582

PublisherSpringer Nature [academic journals on nature.com]


Abstract
Recently, we have characterized the Ras association domain family 1A gene (RASSF1A) at the segment 3p21.3, which is frequently lost in variety of human cancers and epigenetically inactivated in many types of primary tumors, such as lung, breast, kidney, prostate and thyroid carcinomas. Here, we investigated the methylation status of the RASSF1A CpG island promoter in the pathogenesis of pancreatic cancer. RASSF1A hypermethylation was detected in 29 out of 45 (64%) primary adenocarcinomas, in 10 out of 12 (83%) endocrine tumors and in eight out of 18 (44%) pancreatitis samples. In seven out of eight pancreas cancer cell lines, RASSF1A was silenced and was retranscribed after treatment with 5-aza-2'-deoxycytidine. Additionally, we analysed the aberrant methylation frequency of cell cycle inhibitor p16(INK4a) and K-ras gene mutations in the pancreatic samples. p16 inactivation was detected in 43% of adenocarcinomas, in 17% of neuroendocrine tumors, in 18% of pancreatitis and in 63% of pancreas cancer cell lines. K-ras mutations were detected in 16 out of 45 (36%) primary adenocarcinomas. Pancreatic adenocarcinomas with K-ras mutation have significantly less RASSF1A methylation and vice versa (P = 0.001, X-2 test). In conclusion, our data indicate that inactivation of the RASSF1A gene is a frequent event in pancreatic cancer and suggest an inverse correlation between RASSF1A silencing and K-ras activation.



Citation Styles

Harvard Citation styleDammann, R., Schagdarsurengin, U., Liu, L., Otto, N., Gimm, O., Dralle, H., et al. (2003) Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic carcinoma, Oncogene, 22(24), pp. 3806-3812. https://doi.org/10.1038/sj.onc.1206582

APA Citation styleDammann, R., Schagdarsurengin, U., Liu, L., Otto, N., Gimm, O., Dralle, H., Boehm, B., Pfeifer, G., & Hoang-Vu, C. (2003). Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic carcinoma. Oncogene. 22(24), 3806-3812. https://doi.org/10.1038/sj.onc.1206582


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