CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma.

CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Research Abstract Details 

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CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Abstract Text:

Shuji Ogino,Jeffrey A Meyerhardt,Takako Kawasaki,Jeffrey W Clark,David P Ryan,Matthew H Kulke,Peter C Enzinger,Brian M Wolpin,Massimo Loda,Charles S Fuchs,

The CpG island methylator phenotype (CIMP) is a distinct epigenetic phenotype in colorectal carcinoma with concordant methylation in multiple promoter CpG islands. The relationship between CpG island methylation and clinical outcomes among colorectal cancer patients treated with chemotherapy has been a controversial subject. Utilizing real-time polymerase chain reaction (PCR; MethyLight technology), we quantified DNA methylation in 13 CpG island loci (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, MINT1, MINT31, IGFBP3, MGMT, and WRN) in 30 metastatic microsatellite stable colorectal carcinomas in phase I/II clinical trials of combination chemotherapy (5-fluorouracil, irinotecan, leucovorin, and gefitinib). Tumor response was assessed by CT scans performed at baseline and every 6 weeks thereafter. Overall CIMP-high status (either >or=9/13 or >or=7/13 methylated markers; identifying 3 or 5 CIMP-high tumors, respectively) and methylation in CACNA1G, IGF2, MLH1, NEUROG1, RUNX3, MINT31, and WRN were associated with worse survival (all p < 0.01). Although not statistically significant, there was a trend toward resistance to chemotherapy among tumors with CpG island methylation. In conclusion, CpG island methylation may predict poor survival in metastatic microsatellite stable colorectal carcinoma treated with chemotherapy. Additional studies are necessary to examine the role of DNA methylation in treatment efficacy.

CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Publishing Authors By Initials

S Ogino,JA Meyerhardt,T Kawasaki,JW Clark,DP Ryan,MH Kulke,PC Enzinger,BM Wolpin,M Loda,CS Fuchs,

For similar investigative techniques: epidemiologic methods: data collection: vital statistics: mortality: survival rate research abstracts see: investigative techniques: epidemiologic methods: data collection: vital statistics: mortality: survival rate research

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CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Virchows Archiv : an international journal of path

VOLUME: 450

Page Numbers: 529-37

Journal Abbreviation:

ISSN: 0945-6317

DAY: 20

MONTH: 03

YEAR: 2007

CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9423843

CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Keywords Mesh Terms:

KEYWORDS: Survival Rate

MESH TERMS: administration & dosage

Chemical & Substance for Abstract: CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Information

Substance Name: Camptothecin

Registry Number: 7689-03-4

Grant and Affiliation Information for CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma.

AFFILIATION: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. shuji_ogino@dfci.harvard.edu

Country: Germany

AGENCY: United States NCI

GRANT: P01 CA87969-03

ACRONYM: CA

MEDLINETA: Virchows Arch

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