engleski

Genetic Alterations of the E-cadherin Gene Found in Brain Metastases

The work presented in this paper focused on changes of E-cadherin (CDH1) gene in a set of 12 brain metastases. The gene product is a component of adherens junctions, but is also indirectly involved in the Wnt signalling. 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". PCR amplification of tetranucleotide GATA polymorphism (D16S752) linked to CDH1 gene was used to test loss of heterozygosity (LOH) of E-cadherin in brain metastases samples. The marker D16S752 was chosen from the Genome DataBase. Heterozygous samples were visualized on Spreadex EL 300 gels (Elchrom scientific, Switzerland), stained with SyberGold (Molecular Probes, Netherlands). Absence or significant decrease in the intensity of one of D16S752 alleles in metastasis compared to the autologous blood sample was considered as LOH of CDH1 gene. The results of our analysis showed LOH of CDH1 gene in 33% of metastases examined. Five metastases originated from primary lung carcinomas, two from bronchial carcinomas, two from breast carcinomas and three from colon carcinomas. There were 7 male and 5 female patients, and their mean age at diagnosis was 57.6 years. Two LOHs were found in metastases from bronchial carcinomas, one in metastasis from breast carcinoma, and one LOH in metastasis from colon carcinoma. Genetic changes of CDH1 are present in brain metastases that we investigated. 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 regarding this gene on a bigger sample should be performed in future to confirm our suggestion. Novel genes and molecular candidates involved in mechanisms of invasion will offer improvement in comprehension, diagnosis and treatment of these diseases.

E-cadherin; LOH; metastasis

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