Genome-wide screening of DNA copy number alterations in cervical carcinoma patients with CGH+SNP microarrays and HPV-FISH

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Publikace nespadá pod Fakultu sportovních studií, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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KUGLÍK Petr SMETANA Jan VALLOVÁ Vladimíra MOUKOVÁ Lucie KAŠÍKOVÁ Kateřina CVANOVÁ Michaela BROŽOVÁ Lucie

Rok publikování 2014
Druh Článek v odborném periodiku
Časopis / Zdroj International Journal of Clinical and Experimental Pathology
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152070
Obor Genetika a molekulární biologie
Klíčová slova Cervical carcinoma; whole-genome profiling; CGH+SNP microarrays; HPV-FISH; copy number alterations
Popis Alterations in the genome that lead to changes in DNA sequence copy number are characteristic features of solid tumors. We used CGH+SNP microarray and HPV-FISH techniques for detailed screening of copy number alterations (CNAs) in a cohort of 26 patients with cervical carcinoma (CC). This approach identified CNAs in 96.2% (25/26) of tumors. Array-CGH discovered CNAs in 73.1% (19/26) of samples, HPV-FISH experiments revealed CNAs in additional 23.1% (6/26) of samples. Common gains of genetic sequences were observed in 3q (50.0%), 1q (42.4%), 19q (23.1%), while losses were frequently found in 11q (30.8%), 4q (23.1%) and 13q (19.2%). Chromosomal regions involved in loss of heterozygosity were observed in 15.4% of samples in 8q21, 11q23, 14q21 and 18q12.2. Incidence of gain 3q was associated with HPV 16 and HPV 18 positive samples and simultaneous presence of gain 1q (P = 0.033). We did not found a correlation between incidence of CNAs identified by array-CGH and HPV strain infection and incidence of lymph node metastases. Subsequently, HPV-FISH was used for validation of array-CGH results in 23 patients for incidence of hTERC (3q26) and MYC (8q24) amplification. Using HPV-FISH, we found chromosomal lesions of hTERC in 87.0% and MYC in 65.2% of specimens. Our findings confirmed the important role of HPV infection and specific genomic alterations in the development of invasive cervical cancer. This study also indicates that CGH+SNP microarrays allow detecting genome-wide CNAs and copy-neutral loss of heterozygosity more precisely, however, it may be less sensitive than FISH in samples with low level clonal CNAs.
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