| Project/Area Number |
07670213
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | OSAKA CITY UNIVERSITY |
|---|
Principal Investigator |
WAKASA Kenichi Osaka City University, Medical School, Associate professor, 医学部, 助教授 (60158574)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HABA Tomoko Osaka City University, Medical School, Assistant professor, 医学部, 助手 (70281269)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | hepatocellular carcinoma / hepatic neoplasms / adenomatous hyperplasia / clonality / androgen receptor / 肝前癌病変 / 分子生物学 |
|---|
| Research Abstract |
Before treatment of multiple hepatocellular carcinomas (HCCs), identification of the origin of the tumors as either intrahepatic metastases or multicentric occurrences is important. Pathological findings have been used for tentative discrimination. Recently, a polymorphic short tandem repeat was identified at the HUMARA locus of exon 1 of the human androgen receptor gene, which is linked with the X-chromosome. This sequence, consisting of the trinucleotide [CAG]n, is heterozygous in more than 90% of the general population. In this study, we amplify this locus of DNA or mRNA obtained from frozen surgical samples and analyze the clonal origin and multicentricity of HCCs and adenomatous hyperplasia (AH) that seems to be a precancerous lesion by the patterns of X-chromosome inactivation by methylation. Amplification of templates from noncancerous tissues showed that 14 (93%) of the 15 patients were heterozygous at this locus and their tumors could, therefore, be analyzed for clonal origin. All 17 of the HCCs investigated here were monoclonal and both specimens of AH also were monoclonal. Our results suggested that at least some AH is monoclonal in origin and if so, should be monitored carefully or treated. Four patients had multiple HCCs, and the clonal origin of these multiple lesions could be examined. Two patients had lesions of multicentric occurrence and the other two patients seemed to have metastatic lesions. Analysis of the methylation pattern of an X-chromosome-linked locus ; HUMARA must be useful to identify tumors of multicentric occurrence although this method is available in only women.
|
