title: CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas.
abstract: CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance.
authors: Department of Surgical Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China; Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Lifeng
authors: L
authors: Sun
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Angela A
authors: AA
authors: Guzzetta
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Department of Urology; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Department of Gastrointestinal Surgery; Daping Hospital; Third Military Medical University; Chongqing, PR China.
authors: Tao
authors: T
authors: Fu
authors: Department of Surgical Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China; Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Jinming
authors: J
authors: Chen
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Jana
authors: J
authors: Jeschke
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Ruby
authors: R
authors: Kwak
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Rajita
authors: R
authors: Vatapalli
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Stephen B
authors: SB
authors: Baylin
authors: Department of Pathology; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Christine A
authors: CA
authors: Iacobuzio-Donahue
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Department of Oncology; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors: Christopher L
authors: CL
authors: Wolfgang
authors: Department of Surgery; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Department of Oncology; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Department of Urology; The Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Department of Gastrointestinal Surgery; Daping Hospital; Third Military Medical University; Chongqing, PR China.
authors: Nita
authors: N
authors: Ahuja
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012306:Risk; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: CpG island methylator phenotype; DNA methylation; ampullary adenomas; gastrointestinal tumors; sporadic duodenal adenomas