TY - JOUR
T1 - Epigenetic alterations in neuroendocrine tumors
T2 - Methylation of RAS-association domain family 1, isoform a and p16 genes are associated with metastasis
AU - Liu, Lixia
AU - Broaddus, Russell R.
AU - Yao, James C.
AU - Xie, Susu
AU - White, Jill A.
AU - Wu, Tsung Teh
AU - Hamilton, Stanley R.
AU - Rashid, Asif
N1 - Funding Information:
This study was supported by a grant to AR and JCY from Dr and Mrs Raymond R and Beverly Sackler and by Cancer Center Support Grant P30 CA16672 from the National Cancer Institute, National Institute of Health, Department of Health and Human Services.
PY - 2005/12
Y1 - 2005/12
N2 - 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 O 6-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.
AB - 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 O 6-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.
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U2 - 10.1038/modpathol.3800490
DO - 10.1038/modpathol.3800490
M3 - Article
C2 - 16258509
AN - SCOPUS:27944477357
SN - 0893-3952
VL - 18
SP - 1632
EP - 1640
JO - Modern Pathology
JF - Modern Pathology
IS - 12
ER -