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Methylation of the hMLH1 and hMSH2 promoter in early-onset sporadic colorectal carcinomas with microsatellite instability.
Int J Colorectal Dis. 2003 May; 18(3):196-202.IJ

Abstract

BACKGROUND AND AIMS

Microsatellite instability (MSI) occurring from defects in mismatch repair has been found to be associated with about 15% of sporadic colorectal carcinomas. This study examined the incidence of MSI in early-onset sporadic colorectal carcinomas and the role of methylation of the hMLH1 and hMSH2 promoter in sporadic colorectal carcinoma presenting with MSI.

PATIENTS AND METHODS

MSI in 38 early-onset and 40 late-onset sporadic colorectal carcinomas were determined as MSI-H, MSI-L, and MSS using five markers. Methylation of the promoter region in hMLH1 and hMSH2 was assessed using methylation-specific PCR (MSP). Their protein expressions were also identified on immunohistochemical staining.

RESULTS

MSI-H, MSI-L, and MSS were found in six (15.8%), three (7.9%), and 29 (76.3%) cases, respectively, in the early-onset group, and in one (2.5%), five (12.5%), and 34 (85%) cases in the late-onset group. Five cases (71.4%) of MSI-H and two cases (25%) of MSI-L showed methylation of the promoter region in hMLH1. No cases with methylation of the promoter region expressed the hMLH1 protein. Only one case of MSI-H showed methylation of the promoter region in hMSH2 with lack of expression of hMSH2.

CONCLUSION

The mutator pathway in colorectal carcinogenesis appeared more frequently in early-onset than in late-onset colorectal carcinoma. Many cases with MSI in sporadic colorectal carcinoma may be associated with methylation of the promoter in hMLH1.

Authors+Show Affiliations

Department of Surgery, University of Ulsan College of Medicine and Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, 388-1 Poongnap-Dong, Songpa-Ku, Seoul 138-736, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12673483

Citation

Kim, Hee C., et al. "Methylation of the hMLH1 and hMSH2 Promoter in Early-onset Sporadic Colorectal Carcinomas With Microsatellite Instability." International Journal of Colorectal Disease, vol. 18, no. 3, 2003, pp. 196-202.
Kim HC, Kim CN, Yu CS, et al. Methylation of the hMLH1 and hMSH2 promoter in early-onset sporadic colorectal carcinomas with microsatellite instability. Int J Colorectal Dis. 2003;18(3):196-202.
Kim, H. C., Kim, C. N., Yu, C. S., Roh, S. A., & Kim, J. C. (2003). Methylation of the hMLH1 and hMSH2 promoter in early-onset sporadic colorectal carcinomas with microsatellite instability. International Journal of Colorectal Disease, 18(3), 196-202.
Kim HC, et al. Methylation of the hMLH1 and hMSH2 Promoter in Early-onset Sporadic Colorectal Carcinomas With Microsatellite Instability. Int J Colorectal Dis. 2003;18(3):196-202. PubMed PMID: 12673483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylation of the hMLH1 and hMSH2 promoter in early-onset sporadic colorectal carcinomas with microsatellite instability. AU - Kim,Hee C, AU - Kim,Chang N, AU - Yu,Chang S, AU - Roh,Seon A, AU - Kim,Jin C, Y1 - 2002/11/30/ PY - 2002/09/20/accepted PY - 2003/4/4/pubmed PY - 2003/8/9/medline PY - 2003/4/4/entrez SP - 196 EP - 202 JF - International journal of colorectal disease JO - Int J Colorectal Dis VL - 18 IS - 3 N2 - BACKGROUND AND AIMS: Microsatellite instability (MSI) occurring from defects in mismatch repair has been found to be associated with about 15% of sporadic colorectal carcinomas. This study examined the incidence of MSI in early-onset sporadic colorectal carcinomas and the role of methylation of the hMLH1 and hMSH2 promoter in sporadic colorectal carcinoma presenting with MSI. PATIENTS AND METHODS: MSI in 38 early-onset and 40 late-onset sporadic colorectal carcinomas were determined as MSI-H, MSI-L, and MSS using five markers. Methylation of the promoter region in hMLH1 and hMSH2 was assessed using methylation-specific PCR (MSP). Their protein expressions were also identified on immunohistochemical staining. RESULTS: MSI-H, MSI-L, and MSS were found in six (15.8%), three (7.9%), and 29 (76.3%) cases, respectively, in the early-onset group, and in one (2.5%), five (12.5%), and 34 (85%) cases in the late-onset group. Five cases (71.4%) of MSI-H and two cases (25%) of MSI-L showed methylation of the promoter region in hMLH1. No cases with methylation of the promoter region expressed the hMLH1 protein. Only one case of MSI-H showed methylation of the promoter region in hMSH2 with lack of expression of hMSH2. CONCLUSION: The mutator pathway in colorectal carcinogenesis appeared more frequently in early-onset than in late-onset colorectal carcinoma. Many cases with MSI in sporadic colorectal carcinoma may be associated with methylation of the promoter in hMLH1. SN - 0179-1958 UR - https://www.unboundmedicine.com/medline/citation/12673483/Methylation_of_the_hMLH1_and_hMSH2_promoter_in_early_onset_sporadic_colorectal_carcinomas_with_microsatellite_instability_ L2 - https://doi.org/10.1007/s00384-002-0445-0 DB - PRIME DP - Unbound Medicine ER -