MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos

Department/Unit

Center for Natural Sciences and Environment Research

Document Type

Article

Source Title

World Journal of Gatrointestinal Oncology

Volume

13

Issue

12

First Page

2101

Last Page

2113

Publication Date

12-15-2021

Abstract

BACKGROUND

Colorectal cancer (CRC) ranks third in terms of incidence and second in mortality worldwide. In CRC, the silencing of mismatch repair genes, including the mutL homolog 1 (hMLH1) has been linked to microsatellite instability (MSI), the lengthening or shortening of microsatellite repeats. Very limited data have been presented so far on the link of hMLH1 methylation and MSI in Southeast Asia populations with sporadic CRC, and on its clinical significance.

AIM

To investigate the significance of the MSI status and hMLH1 methylation in CRC Filipino patients.

METHODS

Fifty-four sporadic CRC patients with complete clinical data were included in this study. Genomic DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting (HRM) analysis using the Bethesda Panel of Markers (BAT25, BAT26, D2S123, D5S346, and D17S250). hMLH1 methylation screening was performed using bisulfite conversion and methylation specific polymerase chain reaction. Statistical analysis was conducted to calculate their associations to clinicopathological characteristics and survival relevance (Kaplan-Meier curves and the log-rank test).

RESULTS

hMLH1 methylation was observed in 9% and 35% of CRC and normal samples, respectively. Higher incidence of consistently methylated hMLH1 found in both normal and CRC was noticed for relation to location of tumor (P < 0.05). As for MSI status, D2S123 the most common unstable microsatellite and MSI-high (MSI-H) was the most common MSI profile, counted for 46% and 50% of normal and CRC tissues, respectively. The presence of MSI-low (MSI-L) and microsatellite stable (MSS) was 43% and 11% for normal, and 31% and 19% for CRC samples. The mean month of patients’ survival was shorter in patients whose normal and tumor tissues had methylated compared to those with unmethylated hMLH1 and with MSI-H compared to those with MSI-L/MSS (P < 0.05). This was supported by significant difference in Kaplan-Meier with log-rank analysis. This data indicated that hMLH1 methylation and high MSI status have prognostic value.

CONCLUSION

This study showed the clinical significance of hMLH1 methylation and MSI status in sporadic CRC Filipino patients, especially in the normal part of the tumor. Cabral LKD, Mapua CA, Natividad FF, Sukowati CHC, Cortez ER, Enriquez MLD. MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos.

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Keywords

Colon (Anatomy)—Cancer; Methylation; Microsatellites (Genetics)

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