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Volume 124, Issue 5, Pages (May 2003)

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Presentation on theme: "Volume 124, Issue 5, Pages (May 2003)"— Presentation transcript:

1 Volume 124, Issue 5, Pages 1300-1310 (May 2003)
Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas  Sang Geol Kim, Annie On-On Chan, Tsung-Teh Wu, Jean-Pierre J Issa, Stanley R Hamilton, Asif Rashid  Gastroenterology  Volume 124, Issue 5, Pages (May 2003) DOI: /S (03)

2 Figure 1 Examples of evaluation of methylation of p16, p14, and hMLH1 by MSP; and of MGMT, ER, RARβ2, COX2, CAGNAIG, MINT1, MINT2, MINT25, MINT27, and MINT31 by COBRA. The sample numbers are on top of the lanes. N, nonneoplastic tissue; T, tumor; U, PCR using primers for unmethylated alleles; M, PCR using primers for methylated alleles. RKO and SW48 colon cancer cell lines were used as positive controls, and dH2O water without DNA was used as a negative control. Methylated alleles are represented by PCR product in lanes amplified by primers for methylated alleles for genes analyzed by MSP, or by methylated alleles after restriction enzyme digest (arrow) for genes and loci analyzed by COBRA. Gastroenterology  , DOI: ( /S (03) )

3 Figure 2 Methylation status of genes and loci in nonneoplastic mucosa of bile duct and duodenum (left); and methylation status and genetic alterations in biliary, ampullary, and duodenal cancers (right). Sample number is in the right-most column. (A) Tumor-specific genes and loci, (B) genes that are methylated rarely, and (C) genes and loci that are methylated frequently in both nonneoplastic and tumor tissue. The methylation of p16, p14, and hMLH1 genes were analyzed by MSP, and all other genes and loci were analyzed by COBRA. CIMP-high was defined as methylation at 3 or more genes or loci that were methylated more frequently in tumor, CIMP-low as methylation at 1 or 2 loci; and CIMP-negative as methylation at no loci. Gastroenterology  , DOI: ( /S (03) )

4 Figure 3 Percent of tumor samples with CpG island methylation at 13 genes and loci in biliary, ampullary, and duodenal cancers. Genes or loci that are methylated more frequently or have higher methylation densities in duodenal cancers than biliary cancers: p14 (P = 0.04), hMLH1 (P = 0.04), MGMT (P = 0.01), MINT1 (P = 0.02), MINT25 (P = 0.01), MINT27 (P = 0.001), RARβ (P = 0.03), and ER (P = 0.001), respectively; and that are methylated more frequently in duodenal cancers than ampullary cancers: RARβ (P = 0.02) and ER (P = 0.03). Gastroenterology  , DOI: ( /S (03) )

5 Figure 4 The number of methylated genes and loci in bile duct, ampullary, and duodenal cancers used for CIMP classification. The methylation at these genes or loci was dependent on tumor site: 0.7 ± 1.2 for biliary carcinomas, 1.6 ± 1.9 for ampullary carcinomas, and 3.1 ± 2.2 for duodenal carcinomas (P = 0.003). Gastroenterology  , DOI: ( /S (03) )


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