RGD Reference Report - Frequent inactivation of RUNX3 in endometrial carcinoma. - Rat Genome Database

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Frequent inactivation of RUNX3 in endometrial carcinoma.

Authors: Yoshizaki, T  Enomoto, T  Fujita, M  Ueda, Y  Miyatake, T  Fujiwara, K  Miyake, T  Kimura, T  Yoshino, K 
Citation: Yoshizaki T, etal., Gynecol Oncol. 2008 Sep;110(3):439-44. Epub 2008 Jun 24.
RGD ID: 2302555
Pubmed: PMID:18572225   (View Abstract at PubMed)

OBJECTIVE: Our objective was to determine whether RUNX3 tumor suppressor is inactivated in endometrial carcinoma. METHODS: We have investigated 24 endometrial carcinomas, 3 endometrial carcinoma cell lines, and 9 normal endometria for genetic and epigenetic alterations of RUNX3. Reverse-transcription PCR (RT-PCR), methylation-specific PCR (MS-PCR) analysis, and loss of heterozygosity (LOH) analysis were performed. We also tested RUNX3 protein expression by immunohistochemistry. RESULTS: Using RT-PCR technique, we observed a significant loss of RUNX3 mRNA expression in nine of 24 endometrial carcinomas (38%) and in all 3-cell lines (100%). In contrast, all nine of the normal endometria showed an abundant expression of RUNX3 mRNA. Methylation-specific PCR (MS-PCR) analysis of the CpG islands of RUNX3 showed the promoter region to be hypermethylated in 18 of 21 analyzed carcinomas (86%), whereas only two of nine normal endometria (22%) were methylated (p<0.01). By using two polymorphic microsatellite markers, D1S199 and D1S1676, we detected 1p36 LOH in 7 of 21 carcinomas (33%). We observed a significant relationship between the loss of RUNX3 mRNA expression and this regional LOH (p<0.01). Immunohistochemical staining showed that RUNX3 protein expression was lost in 12 of 21 endometrial carcinomas (57%). We observed a significantly more frequent loss of RUNX3 protein expression in the histologically higher-grade tumors (Grade 3) than in Grade 1 or 2 tumors (p<0.01). CONCLUSION: These findings indicate that RUNX3 inactivation may play an important role in carcinogenesis of the endometrium, especially in high-grade endometrial carcinoma.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RUNX3Humanendometrial carcinoma  IAGP DNA:promoter:hypermethylatedRGD 
Runx3Ratendometrial carcinoma  ISORUNX3 (Homo sapiens)DNA:hypermethylation:promoterRGD 
Runx3Mouseendometrial carcinoma  ISORUNX3 (Homo sapiens)DNA:hypermethylation:promoterRGD 

Objects Annotated

Genes (Rattus norvegicus)
Runx3  (RUNX family transcription factor 3)

Genes (Mus musculus)
Runx3  (runt related transcription factor 3)

Genes (Homo sapiens)
RUNX3  (RUNX family transcription factor 3)


Additional Information