Related Experiment Videos
The FHIT gene is alternatively spliced in normal kidney and renal cell carcinoma
1Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Abstract:
FHIT (Fragile Histidine Triad), a putative tumor suppressor gene, was cloned from fetal brain and colon cDNA libraries. Portions of this gene are deleted in esophageal, colon, lung and breast tumors, but this gene has not been found altered in sporadic renal cell carcinomas. We report here an alternatively spliced form of this gene cloned from a kidney cDNA library. This cDNA is 1189 bp in length, and contains an additional 94 bp exon, designated exon 2a (E2a). This novel sequence is located between exon 2 and exon 3 of the FHIT gene's untranslated region and exon 2a is present in all normal kidney tissues and cell lines. Analyses performed on sporadic renal cell carcinoma (RCC) tissues and cell lines, show consistent loss of exon 8 of the FHIT cDNA in almost 60% of the cases. Interestingly, in a familial, as well as, in a metastatic RCC, derived from a patient with the sporadic form, exon 2a and exon 3 are also deleted. Northern analyses with the exon 2a of the familial and the metastatic RCC demonstrates concurrent loss of expression of a 4.4 kb transcript with the loss of the E2a sequence, suggesting that exon 2a of the FHIT gene may play an important role in the oncogenesis of renal cell carcinoma.
Insights
The Fragile Histidine Triad (FHIT) gene, a potential tumor suppressor, shows alterations in various cancers. A novel FHIT exon (2a) deletion is linked to renal cell carcinoma development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The FHIT gene is a candidate tumor suppressor implicated in various cancers.
- Previous studies indicated FHIT alterations in esophageal, colon, lung, and breast tumors, but not sporadic renal cell carcinomas (RCC).
Purpose of the Study:
- To investigate an alternatively spliced form of the FHIT gene in kidney cDNA libraries.
- To determine the role of FHIT alterations, specifically exon 2a, in the oncogenesis of renal cell carcinoma.
Main Methods:
- Cloning of an alternatively spliced FHIT cDNA from a kidney library.
- Analysis of FHIT gene alterations (exon 2a, exon 3, exon 8) in sporadic, familial, and metastatic RCC tissues and cell lines.
- Northern blot analysis to assess FHIT transcript expression.
Main Results:
- An alternatively spliced FHIT cDNA containing a novel exon 2a was identified in kidney tissues.
- Consistent loss of FHIT exon 8 was observed in nearly 60% of sporadic RCC cases.
- Deletion of exon 2a and exon 3, along with loss of a 4.4 kb transcript, was noted in familial and metastatic RCC.
Conclusions:
- The novel FHIT exon 2a is present in normal kidney tissues but frequently lost in RCC.
- Loss of FHIT exon 2a and exon 3, and concurrent transcript expression changes, suggest a significant role in renal cell carcinoma oncogenesis.