Age-dependent alterations in mRNA level and promoter methylation of collagen alpha1(I) gene in human periodontal ligament.

In an attempt to understand the molecular mechanisms of age-dependent degenerative alteration in human periodontal tissues, we examined mRNA level and DNA methylation of collagen alpha1(I) gene. Using healthy periodontal ligament tissues from humans aged 9-76 years, we found that the collagen alpha1(I) mRNA level decreased almost linearly with age. It was observed in both Northern blot and dot blot hybridization.

Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary.

In the present study, we searched for genetic alterations of the entire coding region of PTEN/MMAC1, a recently isolated candidate tumor suppressor gene, in 178 specimens from Japanese patients with various malignant tumors by the polymerase chain reaction-single strand conformation polymorphism method. The samples consisted of 11 glioblastoma multiformes (GBMs), 14 astrocytomas, 47 breast cancers, 25 non-small cell lung cancers, 9 small cell lung cancers, 8 pancreatic cancers, 24 renal cell carcinomas, 20 ovarian cancers, and 20 metastatic lung tumors from various organs. Only one somatic frameshift mutation at codon 319 was observed in one (9%) of eleven GBMs.

IGF2 but not H19 shows loss of imprinting in human glioma.

Genomic imprinting is a gamete-specific modification resulting in the allele-specific expression of genes in somatic cells. A loss of imprinting (LOI) has been found in many embryonal and adult tumors, suggesting that it plays a role in tumor development. The incidence of LOI, however, does not seem to be ubiquitous among tumors because neuroblastoma and colorectal cancer revealed no LOI.

Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver.

The state of DNA methylation in the c-fos gene was examined in human livers of different ages, cirrhosis and hepatocellular carcinoma. The degree of methylation in the intron 1 to exon 4 region increased with age, whereas all of the 10 cirrhosis samples revealed a decrease in methylation when compared to normal livers of similar ages. The 11 hepatocellular carcinomas showed varied alterations suggesting that the alteration of the c-fos gene methylation is related to aging as well as to early-step of hepatocarcinogenesis.

Alteration of c-fos gene methylation in human gliomas.

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development.