Related Experiment Videos
Methylation of the RASSF1A gene in human cancers
Gerd P Pfeifer1, Jung-Hoon Yoon, Limin Liu
1Department of Biology, City of Hope Medical Center, Duarte, CA 91010, USA.
Abstract:
Loss of genetic material from chromosome 3p21.3 is one of the most common and earliest events in the pathogenesis of lung cancer and many other solid tumors. The chromosomal area 3p21.3 is thought to harbor at least one important tumor suppressor gene, which, despite many years of investigation, has remained elusive. In our previous studies, we have identified and cloned a gene from the common homozygous deletion area at 3p21.3. The gene, named RASSF1A (Ras ASSociation domain Family 1A), has homology to a mammalian Ras effector. The RASSF1A gene is epigenetically inactivated in a large percentage of human lung cancers, in particular small cell carcinomas. A high frequency of methylation of RASSF1A is found also in breast cancers, renal cell carcinomas, ovarian, gastric and bladder cancers, and in neuroblastomas. The RASSF1A gene is a candidate for a tumor suppressor gene in 3p21.3.
Insights
Loss of chromosome 3p21.3 material is common in tumors. Researchers identified the RASSF1A gene, a candidate tumor suppressor, which is epigenetically inactivated in many lung and other cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosome 3p21.3 deletions are early events in lung cancer and solid tumor pathogenesis.
- This region is suspected to contain a crucial tumor suppressor gene that has yet to be definitively identified.
- Previous research has focused on identifying genes within this commonly deleted chromosomal area.
Purpose of the Study:
- To identify and clone a candidate tumor suppressor gene from the 3p21.3 common deletion region.
- To investigate the role of the identified gene in the development of various cancers.
Main Methods:
- Gene identification and cloning from the 3p21.3 homozygous deletion region.
- Sequence analysis to determine homology to known effector proteins.
- Epigenetic analysis, specifically methylation status, in tumor samples.
Main Results:
- The RASSF1A (Ras ASSociation domain Family 1A) gene was identified and cloned.
- RASSF1A exhibits homology to mammalian Ras effectors.
- Epigenetic inactivation, primarily through methylation, of RASSF1A was observed in a significant percentage of lung cancers (especially small cell carcinomas), as well as breast, renal, ovarian, gastric, bladder cancers, and neuroblastomas.
Conclusions:
- RASSF1A is a strong candidate for the elusive tumor suppressor gene located at chromosome 3p21.3.
- The epigenetic inactivation of RASSF1A is a frequent event in multiple human cancers, highlighting its role in tumorigenesis.