Naslov
Multivariate statistical analysis of the molecular data on APC and CDH1 genes' involvement in renal cell carcinoma and clinical parameters of the disease.

Autori
Pećina-Šlaus, Nives ; Gall-Trošelj, Koraljka ; Pavelić, Krešimir ; Pavelić, Jasminka

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

Izvornik
Abstracts of the 13th Ljudevit Jurak International symposium on comparative pathology / - , 2002

Skup
Ljudevit Jurak International symposium on comparative pathology (13 ; 2002)

Mjesto i datum
Zagreb, Hrvatska, 07.06.2002. - 08.06.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
APC; CDH1; renal cell carcinoma

Sažetak
When investigating cancer at the molecular level, data obtained by methods of molecular biology are usually compared and correlated with only one clinical parameter at the time resulting in one-dimensional approach to statistical analysis. The employment of multivariate statistical methods simultaneously correlates and weights all investigated parameters offering new insights into the problem. In this paper the data that we obtained investigating renal cell carcinoma (RCC) at the molecular level were analyzed by multivariate statistical method (Principal components) together with clinical parameters: TNM stage, histopathological grade, age and sex. Forty-five human renal cell carcinomas were tested for adenomatous polyposis coli tumor suppressor gene (APC) instability by polymerase chain reaction/loss of heterozygosity (LOH) using RFLP method. E-cadherin gene (CDH1) was analyzed by PCR amplification of tetranucleotide marker (D16 S752) and the alleles were visualized by PAGE/silver staining. The overall proportion of LOH cases of the APC gene was 37.5% (9/24). D16 S752 marker linked to E-cadherin gene (informativity 91%) revealed 3 (7.5%) LOH cases. In 10% of RCC samples another type of genomic instability was detected, replication error (RER) indicating that another cellular mechanism, mismatch repair, is targeted in RCC. The results of the multivariate statistical analysis of samples informative for both APC and E-cadherin genes showed that in this data set LOH of the APC gene is positively correlated with advanced age and more severe TNM stages. Genomic instabilities of the E-cadherin gene, on the other hand, appear to be correlated with younger age groups and less severe TNM stages. Our results suggest that alterations in APC gene are not the first event in kidney tumorigenesis, but are involved in progression of RCC. Analysis of E-cadherin involvement although less conclusive (because of lower frequency to APC changes) suggest that changes in this gene may be an earlier event. Given that E-cadherin is involved in diverse mechanisms in the cell it is also possible that the impairment of its function lies in transcriptional mechanisms.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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