Naslov
BRCA1 and BRCA2 sequence variants in healthy women in Croatia analyzed by high-resolution melting and in silico analysis of variants of unknown clinical significance

Autori
Levanat, Sonja ; Levačić Cvok, Mirela ; Čretnik, Maja, Musani, Vesna ; Ozretić, Petar

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

Izvornik
European Journal of Cancer Supplements / Smyth, John - Amsterdam : Elsevier, 2008, 98-98

Skup
20th Meeting of the European Association for Cancer Research

Mjesto i datum
Lyon, Francuska, 05.07.2008. - 08.07.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
BRCA1; BRCA2; high-resolution melting analysis

Sažetak
BRCA1 and BRCA2 are the major hereditary breast and/or ovarian cancer predisposing genes and their mutations increase the risk of developing cancer. Mutations in either of these tumor suppressor genes are associated with both sporadic and hereditary forms of breast cancer. At least ten percent of cases are attributed to familial inheritance. In Croatia, more than 2200 new cases of breast cancer are diagnosed each year, and about 900 women die of this malignancy. We analyzed the distribution and occurance of sequence variants in BRCA1 and BRCA2 genes on a healthy population of women in Croatia in an attempt to distinguish non-tumorigenic from tumorigenic changes in genomic sequences of BRCA1 and BRCA2 genes. The screening was performed by high resolution melting approach, which is based on differences in melting curves caused by variants in nucleotide sequence ; detected variants were confirmed by sequencing. In total we analyzed 230 samples for BRCA1 gene and 140 samples for BRCA2 gene. We found 21 different sequence variantsin BRCA1 (2 novel) and 36 variants in BRCA2 gene (7 novel). At present, almost half of all BRCA1 and BRCA2 sequence variants found are unclasified variants (UVs) so their clinical significance is unknown or uncertain. That represents problem for risk assesment in genetic counseling. After reveaing BRCA1 and BRCA2 sequence variants in healthy Croatian females, our aim was to find fast in silico method for assesing preliminary clinical significance of UVs newly found in patients. We used different publicly available programs and web-based tools to identify UVs that may have deleterious effects with respect to different biomolecular functional categories (splicing regulation, transcriptional regulation, nonsynonimous amino acid SNP effect ...) so their clinical significance in cancer ethiology could be assumed. we have found that several sequence variants with nonsynonymous amino acid changes ( silent mutations) could have impact on splicing regulation by disrupting exonic splice enhancers. Intronic sequence variants showed no potential impact on splicing because nucleotide changes at that positions likely make no changes in consensus splice site.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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