Caracterización de alteraciones moleculares en tumores de endometrio

[EN]Commonly mutated gene in endometrial carcinoma (EC) are PTEN, PIK3CA, KRAS, BRAF, ß-catenin, p53, p16 and E-cadherin, all belonging to intracellular signaling related to growth, differentiation, apoptosis, etc. We have identified PTEN mutations in 57.1% of cases, 19% in PIK3CA, KRAS 14.3%, 19% in CTNNB1, p53 23.8%, 4.8% and 2.4% in CDH1 in p16. We analyzed the nature of mutations in PTEN, PIK3CA and p53 to verify the membership of the alleles, LOH and protein expression. Defects in DNA MMR system produces accumulation of mutations throughout the genome. We have studied MSI with 8 markers and analyzed the hMLH1 and hMSH2 genes. 63.6% of cases had MSI, 4.8% mutations in hMLH1, hMSH2 mutations in 2.4% and 9.5% large deletions. hMLH1 was methylated in 38.1% of cases, hMSH2 hMSH6 in 21.4% and 26.2%. HDAC involved in post-transcriptional modifications of the nucleosomes. Expression in EC is heterogeneous. 14.3% of the patients had truncating mutations in exon 1 of HDAC2. 60.5% of cases had normal expression or overexpression of HDAC, no expression in HDAC1 and HDAC3 in 13.2%, no expression in HDAC2 and HDAC3 at 7.9%, not HDAC1 and HDAC2 expression in 5.2%, non-expression of HDAC1 at 2.6%, and no expression of the three proteins at 7.9%. These results confirm the discrimination of CHD by their genetic profile. Alterations in the MMR system genes are associated with mutations in PTEN through hypermethylation of hMLH1 and not to the presence of MSI. The differences in the expression of HDACs have no correlation with tumor type, although mutations in HDAC2 if they relate to alterations in the MMR system

Author

• Núñez Lozano, Mercedes

• Tesis y disertaciones académicas
• Universidad de Salamanca (España)
• Academic dissertations
• Medicina molecular
• Tumores

Identifier

hdl:10366/83304

OAI identifier oai:identifier

oai:gredos.usal.es:10366/83304