Scholarship 08/05489-0 - Biologia molecular, Neoplasias colorretais - BV FAPESP
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Expression profiling in sporadic adenomas of the colorectum and its correlation with K-ras and BRAF mutation, hMLH1 and MGMT methylation and protein expression of DNA gene repair

Grant number: 08/05489-0
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: November 01, 2008
End date until: October 31, 2012
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Renata de Almeida Coudry
Grantee:Ligia Petrolini de Oliveira
Host Institution: Hospital A C Camargo. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

TP53 gene is located in the short arm of the chromosome 17 and encodes a protein that prevents cells from accumulating DNA damage by induction of pathways leading to cell arrest or apoptosis. TP53 mutations are found in approximately 50% of human cancers. While most of tumor suppressor genes are inactivated by mutation leading to absence of protein synthesis, more than 80% of TP53 alterations are missense mutations that lead to the synthesis of a stable full-length protein. Another important group of point mutations observed in TP53 gene are silent mutations, that is those that change one codon for another synonymous one, and for this reason do not affect the coding meaning gene, but appears also to be related to cancer. Synonymous mutation may alter gene function by causing aberrant splicing signals. It has been proposed that alterations in the regulating splicing regions can result in deleterious effects in the pre-mRNAs. Although some studies have demonstrated that synonymous mutation is a common finding in cancer, few studies were done to investigate an intrinsic correlation with the tumorigenic process. Thus, the aim of this study is to correlate the presence of aberrant splicing and synonymous mutation in colorectal cancer. It is known that colorectal cancer shows around 70% alteration in TP53 gene, this way is a suitable neoplasia to better understand aberrant splicing and synonymous mutation related with carcinogenesis.

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