The hMLH1 gene plays an essential role in DNA repair. Methylation of the hMLH1 gene is common in many types of cancer and can lead to the loss of hMLH1 expression. However, the association and clinicopathological significance between hMLH1 promoter hypermethylation and non-small-cell lung cancer (NSCLC) is elusive. Here, we investigated the correlation of hMLH1 promoter hypermethylation and NSC...

Microsatellite instability (MSI) is a characteristic feature of hereditary nonpolyposis colorectal cancer and is also observed in sporadic colorectal and endometrial cancers. Alterations in the mismatch repair genes hMLH1 and hMSH2 are important for the development of MSI. It has recently been demonstrated that hypermethylation of the hMLH1 promoter region is associated with MSI and appears to ...

Most sporadic gastric cancer with the microsatellite instability (MSI) phenotype is linked with hypermethylation (HM) of hMLH1. However, a part of gastric cancer with hMLH1 HM does not show MSI, suggesting a region-specific effect of hMLH1 promoter methylation on developing MSI. To test this possibility, we measured the methylation level in 3 distinct areas of hMLH1 promoter and compared them w...

Microsatellite instability (MSI) is caused mainly by dysfunction of hMLH1, where aberrant hypermethylation (HM) of its promoter region is involved. Previously, we suggested that HM in the proximal region of the hMLH1 promoter plays a critical role in progression of gastric cancer with MSI and this specific region should be analyzed for diagnostic use of hMLH1 HM. We expanded the analyses of hML...

Mutations of DNA mismatch repair genes, including the hMLH1 gene, have been linked to human colon and other cancers in which defective DNA repair is evidenced by the associated instability of DNA microsatellite sequences (MSI). Germ-line hMLH1 mutations are causally associated with inherited MSI colon cancer, and somatic mutations are causally associated with sporadic MSI colon cancer. Previous...

Patients with sporadic microsatellite instable colorectal cancers, in most of which the function of the hMLH1 mismatch repair gene is impaired, do not gain a survival benefit from 5-fluorouracil (5-FU)-based chemotherapy. However, the effect of hMLH1 on the cytotoxicity induced by 5-FU has not yet been sufficiently confirmed. In this study, we assessed the effect of hMLH1 on cytotoxicity and ap...

AIMS AND BACKGROUND The mechanism of human MutL Homolog (hMLH1) gene transcriptional inactivation in non-small cell lung cancer (NSCLC) is still unclear. The aim of this study is to further investigate the main mechanism of hMLH1 gene inactivation in NSCLC samples of Chinese patients. METHODS AND STUDY DESIGN This study was performed in surgically resected primary tumor and matched normal tis...

BACKGROUND Both hMSH2 and hMLH1 are integrated in the DNA mismatch repair (MMR) system. Reduced expression of these proteins has been reported in head and neck carcinoma; however, few studies have examined the normal levels of these proteins in oral tissues or investigated factors which could interfere with this expression. The aim of this study was to detect the expression pattern of hMSH2 and...

BACKGROUND Cisplatin-based chemotherapy can cure more than 80% of metastatic germ-cell testicular tumors (GCTs). The response to cisplatin-based chemotherapy has been related to Microsatellite Instability (MSI), which is caused by genetic or epigenetic changes in genes of the DNA Mismatch Repair (MMR) pathway. PATIENTS AND METHODS We investigated 15 refractory and 36 chemosensitive GCTs for i...

BACKGROUND Mammalian mismatch repair system is responsible for maintaining genomic stability during repeated duplications, and human MutL homolog 1 (hMLH1) protein constitutes an important part of it. Various isolated studies have reported the altered expression of hMLH1 in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Research is lacking in the quantitative estimation and comp...