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Impaired FHIT expression characterizes serous ovarian carcinoma
K Ozaki1, T Enomoto, K Yoshino
1Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Osaka, Japan.
Abstract:
The FHIT (fragile histidine triad) gene on chromosome 3p14.2 is a candidate tumour suppressor gene. To define the role of the FHIT gene in the development of ovarian cancer, we have examined 33 ovarian carcinomas, 2 borderline tumours and 10 benign adenomas for the presence of FHIT gene alterations. FHIT transcripts were analysed by RT-PCR and sequencing. Aberrant FHIT transcripts were observed in 5/33 carcinomas (15%) and in 1 of 2 borderline tumours. Loss of normal FHIT transcript was observed in 5/33 carcinomas (15%) but not in 2 borderline tumours or 10 benign adenomas. Allelic losses at D3S1300 and D3S4103, both located within intron 5 of FHIT, were detected in 5/24 (21%) and 5/25 (20%) informative ovarian carcinomas, respectively. Expression of Fhit protein was analysed by immunohistochemistry in 44 carcinomas, 19 borderline tumours and 16 benign adenomas. Loss or significantly reduced expression of Fhit protein was observed in 6/44 (14%) ovarian carcinomas but not in any of 19 borderline tumours or 16 benign adenomas. The impaired Fhit protein expression was significantly correlated with the loss of normal FHIT transcription. Most notably, loss of normal FHIT transcript and impaired expression of Fhit protein occurred only in serous adenocarcinomas of grade 2 and 3 (5/15; 33% and 6/19; 32%, respectively). The present data suggest that inactivation of the FHIT gene by loss of expression is one of the important molecular events associated with the genesis of ovarian carcinoma, especially of high-grade serous carcinoma.
Insights
The fragile histidine triad (FHIT) gene shows alterations in ovarian cancer, with loss of expression linked to high-grade serous carcinomas. This suggests FHIT gene inactivation is crucial in ovarian cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The fragile histidine triad (FHIT) gene, located at 3p14.2, is a potential tumor suppressor.
- Ovarian cancer development involves genetic alterations, but the specific role of FHIT remains to be fully elucidated.
Purpose of the Study:
- To investigate the alterations and expression patterns of the FHIT gene in various types of ovarian tumors.
- To determine the correlation between FHIT gene status and ovarian carcinoma progression, particularly in serous subtypes.
Main Methods:
- Analysis of FHIT gene transcripts using RT-PCR and sequencing in 33 ovarian carcinomas, 2 borderline tumors, and 10 benign adenomas.
- Assessment of allelic losses at FHIT-linked microsatellite markers (D3S1300, D3S4103) in informative ovarian carcinomas.
- Immunohistochemical analysis of Fhit protein expression in 44 ovarian carcinomas, 19 borderline tumors, and 16 benign adenomas.
Main Results:
- Aberrant FHIT transcripts were found in 15% of carcinomas and 1 of 2 borderline tumors; loss of normal transcript occurred in 15% of carcinomas.
- Allelic losses within FHIT intron 5 were detected in approximately 20% of informative ovarian carcinomas.
- Loss or significant reduction of Fhit protein expression was observed in 14% of ovarian carcinomas, correlating with impaired FHIT transcription, and was notable in high-grade serous adenocarcinomas (33-32%).
Conclusions:
- FHIT gene inactivation, characterized by loss of expression, is a significant molecular event in ovarian carcinoma pathogenesis.
- The findings highlight the specific involvement of FHIT gene alterations in the development of high-grade serous ovarian carcinomas.
- Loss of FHIT expression is a potential biomarker for advanced ovarian cancer stages.