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- Title
Epigenetic alterations in neuroendocrine tumors: methylation of RAS-association domain family 1, isoform A and p16 genes are associated with metastasis.
- Authors
Lixia Liu; Broaddus, Russell R.; Yao, James C.; SuSu Xie; White, Jill A.; Tsung-Teh Wu; Hamilton, Stanley R.; Rashid, Asif
- Abstract
Well-differentiated neuroendocrine tumors including pancreatic endocrine tumors and carcinoid tumors are uncommon neoplasms that have site-specific differences in clinicopathological features, clinical course and genetic alterations. The epigenetic alterations in these tumors are not well characterized. We therefore compared methylation of the RAS-association domain family 1, isoform A (RASSF1A), p14, p16 and O6-methyl-guanine methyltransferase genes in neuroendocrine tumors from 47 patients including 16 pancreatic, 15 nonileal and 16 ileal neuroendocrine tumors. Methylation of the RASSF1A gene was present in 57% of tumors, p14 in 49%, p16 in 26% and O6-methyl-guanine methyltransferase in 13% of tumors. Ileal neuroendocrine tumors lacked methylation of O6-methyl-guanine methyltransferase gene (P=0.04). RASSF1A methylation was associated with histopathologic type of tumors (P=0.03) and lymph node metastasis (P=0.004), and p16 methylation with older patient age (P=0.002) and liver metastasis (P=0.04). Two or more genes were methylated in 53% of tumors, one gene was methylated in 30% of tumors, and all four genes were unmethylated in 17% of tumors. Methylation of one or more gene was associated with older age of patients (P=0.01), and methylation of two or more genes was associated with liver metastasis (P=0.044). Our study shows that in neuroendocrine tumors epigenetic alterations vary by tumor subsite and clinicopathologic features, including age of onset, histopatholoic type and metastasis status.Modern Pathology (2005) 18, 1632–1640. doi:10.1038/modpathol.3800490; published online 7 October 2005
- Subjects
NEUROENDOCRINE tumors; CANCER invasiveness; ABDOMINAL tumors; CYSTS (Pathology); LYMPH nodes; ONCOLOGY
- Publication
Modern Pathology, 2005, Vol 18, Issue 12, p1632
- ISSN
0893-3952
- Publication type
Article
- DOI
10.1038/modpathol.3800490