Inactivation patterns of p16/INK4A in oral squamous cell carcinomas

The p16/INK4A is one of the major target genes in carcinogenesis and its inactivation has frequently been reported in other types of tumors. The purpose of this study is to evaluate inactivation patterns of p16/INK4A in oral squamous cell carcinoma. Six different oral cancer cell lines, SCC-4, SCC-9, SCC-15, SCC-25, KB, and SNUDH- 379 were examined for inactivation of p16/INK4A genes. In the analysis of p16/INK4A gene inactivation, PCR amplification, direct sequencing, and methylation-specific PCR methods were adopted for evaluation of homozygous deletion, point mutation, and promoter hypermethylation, respectively. Homozygous deletion was detected in SCC-25 and SCC-9. SCC-15 showed hypermethylated promoter region within p16/INK4A gene. It is suggestive in the present study that inactivation patterns of p16/INK4A were mainly homozygous deletion, promoter methylation rather than point mutation in oral squamous cancer cell lines, so treatment modalities of oral squamous cell carcinoma should be focused on these types of inactivation.

A Study on the Correlation between the Polymorphism of GSTM1 and GSTT1 Genes and Susceptibility to the Development of COPD / 中国医师杂志

Objective To study the correlation between the polymorphism of GSTM1 and GSTT1 genes and the susceptibility to the development of COPD. Methods Polymerase chain reaction (PCR) was used to detect the GSTM1 and GSTT1 genotypes in 91 cases of the patients with COPD (COPD group) and 44 cases of the subjects without COPD (control group), and their susceptibility to the development of COPD were analyzed according to their gender, age and smoking history. Results There was significant difference in the frequency of GSTM1 0/0 genotype between the two groups of male persons with more than 40 years old (P

Homozygous Deletion of p16INK4 and p15INK4B Genes in Human Advanced Ovarian Carcinoma / 대한산부인과학회잡지

OBJECTIVE: p16INK4 and p15INK4B genes are known to be tumor suppressor genes which reside in p21 region of chromosome 9 and are related to cell cycle control as an inhibitor of cyclin-dependent-kinase. We designed this study to search for deletion and decreased expression of p16INK4 and p15INK4B genes in advanced ovarian carcinomas. METHODS: Polymerase chain reaction (PCR)-based analysis was performed to search for deletion of p16INK4 and p15INK4B using DNA extracted from frozen tissue in liquid nitrogen of thirty-one advanced ovarian carcinoma patients. The intensities of PCR bands were analyzed using an imaging densitometer to determine gene dosage in tumor samples and the relative gene dosage was calculated by comparing band intesity of p16INK4 or p15INK4B with that of beta-globin gene. Homozygous deletions were assigned to tumors in which the ratio was reduced to less than 25% in any one of exons of p16INK4 and p15INK4B. Immunohistochemical techniques were used to study the expression of p16INK4. p16-negative cells were characterized by the absence of nuclear staining, whereas cytoplasmic staining was variable. Clinico-pathologic features, complete remission rates and survivals were analyzed according to the status of p16INK4 and p15INK4B genes. RESULTS: Homozygous deletion of p16INK4 was detected in 12.9% of advanced ovarian carcinoma patients and that of p15INK4B in 35.5%. Clinico-pathologic features such as FIGO stage, histological grade, serum CA-125 levels were not different from groups with homozygously deleted p16INK4 and p15INK4B to those with normal genes. The survival of patients (13 [6-20] months) with homozygously deleted p16INK4 was significantly shorter than that (30 [8-52] months) of patients with normal p16INK4 (p=0.046; Log-rank test). CONCLUSION: These observations indicate that deletions of p16INK4 and p15INK4B gene might be involved in tumorigenesis of ovarian carcinoma and could be useful as a prognostic factor. A prospective, controlled study with more patients will be mandatory in the future.

The p16INK4A Expression in Stomach Cancer , Colon Cancer and Hepatoma Cell Lines / 대한암학회지

PURPOSE: The p16(INK4A) gene encodes a specific inhibitor of cell cycle progression. In recent years, genetic deletion and altered expression of p16(INK4A) gene were frequently showed in many human cancers. So, the p16(INK4A) gene is considered as tumor suppressor gene. However, there has been a few data for the p16(INK4A) in gastric cancer, colon cancer, and hepatoma.So.we investigated the genetic deldtion and altered expression of p16(INK4A) in gastric cancer, colon cancer and hepatoma cell lines. MATERIALS AND METHODS: The homozygous deletion of p16(INK4A) was examined by using PCR and the protein expression of p16(INK4A) by using Western blotting in cancer cell lines established from Korean patients: stomach cancer, colon cancer and hepatoma cell lines. RESULTS: Homozygous deletion of p16(INK4A) was detected only 1 stomach cancer cell line out of 13 cell lines examined. The p16(INK4A) was detected in 3 of 13 cancer cell line. These results showed the low frequency of p16(INK4A) homozygous deletion and high frequency of p16(INK4A) expression alteration in stomach cancer, colon cancer and hepatoma cell lines. CONCLUSION: In this study, it may be suggested that the altered pl6(INK4A) expression as well as p16(INK4A) gene deletion play important role in oncogenesis. Further studies to determine the mechanism of p16(INK4A) gene inactivation are expected.

Analysis of p16 gene deletion and mutation in gastric carcinoma / 中国病理生理杂志

AIM: To investigate p16 gene alterations in gastric carcinoma. METHODS: 36 fresh tumor specimens taken from gastric cancer patients were analyzed for p16 gene deletion and mutation by polymerase chain reaction (PCR) and DNA sequencing. RESULTS: Homozygous deletion of exon 1 and exon 3 was observed in 2 cases and 3 cases of diffuse carcinoma, respectively. The frequency of homozygous deletion was 13.89%. No p16 gene point mutation was detected. CONCLUSION: The deletion of p16 genes may be related to gastric carcinogenesis.