title: Genome-wide screening of DNA copy number alterations in cervical carcinoma patients with CGH+SNP microarrays and HPV-FISH.
abstract: 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.
authors.affiliation: Laboratory of Molecular Cytogenetics, Institute of Experimental Biology, Faculty of Science, Masaryk University Brno, Czech Republic ; Department of Medical Genetics, University Hospital Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kuglik
authors.affiliation: Laboratory of Molecular Cytogenetics, Institute of Experimental Biology, Faculty of Science, Masaryk University Brno, Czech Republic ; Department of Medical Genetics, University Hospital Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Smetana
authors.affiliation: Laboratory of Molecular Cytogenetics, Institute of Experimental Biology, Faculty of Science, Masaryk University Brno, Czech Republic ; Department of Medical Genetics, University Hospital Brno, Czech Republic.
authors.forename: Vladimira
authors.initials: V
authors.lastname: Vallova
authors.affiliation: Department of Gynecological Oncology, Masaryk Memorial Cancer Institute Brno, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Moukova
authors.affiliation: Laboratory of Molecular Cytogenetics, Institute of Experimental Biology, Faculty of Science, Masaryk University Brno, Czech Republic ; Department of Medical Genetics, University Hospital Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kasikova
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine and Faculty of Science, Masaryk University Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Cvanova
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine and Faculty of Science, Masaryk University Brno, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Brozova
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000821:virology; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
keywords: CGH+SNP microarrays; Cervical carcinoma; HPV-FISH; copy number alterations; whole-genome profiling