Naslov
Analysis of WNT Signaling Pathway Genes in Brain Metastases

Autori
Zeljko, Martina ; Pećina-Šlaus, Nives ; Majić, Željka ; Nikuševa Martić, Tamara ; Tomas, Davor ; Beroš, Vili

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Regional multidisciplinary biomedical workshop (RMBW) on cell imaging in neurology (medicine) and neuroscience Molecular Morphology in Neuroscience Workshop : Abstract book : COST Action B30 : Neural Regeneration and Plasticity NEREPLAS / Andjus, Pavle R ; Gajović, Srećko - Zagreb, 2008, 29-29

Skup
Regional multidisciplinary biomedical workshop (RMBW) on cell imaging in neurology (medicine) and neuroscience Molecular Morphology in Neuroscience Workshop : COST Action B30: Neural Regeneration and Plasticity NEREPLAS

Mjesto i datum
Opatija, Hrvatska, 04.12.2008. - 07.12.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
brain metastases; wnt signaling; APC gene; CDH1 gene

Sažetak
The work presented in this paper focused on changes of E-cadherin (CDH1), beta-catenin and APC genes in a set of 26 brain metastases. All gene products are involved in the Wnt signaling. Loss of function of E-cadherin tumor-suppressor protein correlates with increased invasiveness and metastasis of tumors, resulting in it being referred to as the "suppressor of invasion gene". APC is a negative regulator of wnt signaling and beta-catenin is the main signaling molecule that in response to wnt signaling enters the nucleus and activates target genes. PCR amplification of tetranucleotide GATA polymorphism (D16S752) linked to CDH1 gene was used to test loss of heterozygosity (LOH) of E-cadherin. MspI/RFLP method was used to test LOH of APC gene and heteroduplex method was used to investigate potential mutations in beta-catenin. Absence or significant decrease in the intensity of one of the alleles in metastases compared to the autologous blood sample was considered as LOH of relevant genes. The results of our analysis showed LOH of CDH1 gene in 15, 4% of metastases examined. LOH of APC gene was found in 36.4% of informative samples. Interestingly no mutation was found in beta-catenin’ s exon 3, that has been reported as mutational hot-spot. Ten metastases originated from primary lung carcinomas, four from bronchial carcinomas, five from breast carcinomas, four from colon carcinomas, two from renal and one from gastric carcinoma. There were 15 male and 11 female patients, and their mean age at diagnosis was 61.7 years. Two LOHs of CDH1 gene were found in metastases from bronchial carcinomas, one in metastasis from breast carcinoma, and one LOH in metastasis from colon carcinoma. Conclusion. Genetic changes of CDH1 and APC genes are present in brain metastases that we investigated, while mutational hot-spot of beta-catenin was not targeted for mutations. Our findings may contribute to better understanding of brain metastases’ genetic profile. We consider our finding a small but relevant contribution to understanding pathophysiological mechanisms of brain metastases formation. Further investigation on a bigger sample should be performed in future to confirm our suggestions.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA