Abstract LB-380: Distinct methylation pattern in early-onset colorectal cancer patients without detectable germline mutation
| Autor: | Anthony K W Chan, Suet Yi Leung, Wendy Wy Tsui, Carmen Li, Tsun-leung Chan, S. T. Yuen, Annie Sy Chan |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cancer Research. 72:LB-380 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Colorectal cancer (CRC) is currently the second most common cancer and mortality rate of all cancers in Hong Kong. We have previously reported a higher incidence of early-onset colorectal cancer patients compare with other ethnic groups, which may be caused by genetic or epigenetic predisposition in the Chinese population. Despite we confirmed Lynch Syndrome (LS) plays a significant role in it, pathogenic event of roughly 20% of young patients with MSI tumour cannot be identified. These patients are still susceptible to novel genetic or epigenetic predisposition of CRC. In this study, we compared the epigenetic signature of CRC patients below and above the age of 50 years old, who developed High level of microsatellite instability (MSI-H) and loss of MLH1 expression. The CpG island methylator phenotype (CIMP), regional methylation events, Braf and Kras mutation status have been examined. Among 12 cases of the early-onset patients, unexpectedly 5 of them showed constitutive MLH1 promoter hypermethylation versus 1 in 26 cases of the late-onset control patients by pyrosequencing (p-value < 0.01). CIMP-High status, which has been frequently reported in late-onset patients, was found to be 25% and 77% in the early and late-onset groups respectively (p value < 0.001). Strikingly, regional methylation coincides with the CIMP-High cases and MLH1 promoter methylation was the unique epimutation event in the chromosomal region encompass MLH1 in most of the early-onset patients. We are the first to demonstrate that CIMP status and MLH1 regional methylation are a distinct phenotype in the patient with early-onset CRC irrespective of the constitutive status of MLH1 promoter methylation event. Our data suggest that the tumorigenesis of early-onset CRC is significantly different from patients with late-onset CRC despite they are all classified as MSI-H and loss of expression of MLH1. Lastly, epigenetic signature of most of the early-onset CRC patients is indistinguishable from the patient with constitutive MLH1 promoter methylation. It is unclear epigenetic predisposition contribute to the high incidence of early-onset CRC. Further investigation for additional markers should be performed as routine Kras and Braf mutation status were uninformative. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-380. doi:1538-7445.AM2012-LB-380 |
| Databáze: | OpenAIRE |
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