Genomic rearrangements involving rDNA and centromeric heterochromatin in vulvar epidermoid carcinoma cell line A-431.
The cytogenetic and molecular cytogenetic characterization of the human cell line A-431 derived from a vulvar epidermoid carcinoma is presented. A combination of karyotyping, fluorescence in situ hybridization (FISH) with chromosome- and/or region-specific probes, M-FISH, RxFISH, and comparative genomic hybridization (CGH) analysis was used. Six marker chromosomes with rearrangements involving insertions of single or double nucleolar organizing regions (NORs) and/or homogeneously staining regions containing active and overexpressed NORs and regions of centromeric heterochromatin were found: der(6), der(7), der(17), der(21), dic(13;14), and dic(14;18). The chromosomal origin of 14 other marker chromosomes was elucidated. Amplification of the C-MYC oncogene at 8q24 was revealed in two marker chromosomes: dup(8)(q24) and der(15)t(8;15)(q22;p11). Confirming previous reports, amplification of the cyclin D1 gene within an abnormal chromosome 11, that is, der(11)t(7;11)(p15;q21), was also detected. Loss of the TP53 tumor suppressor gene was evidenced over two der(17). Good concordance was found among karyotyping, FISH analysis, and CGH. Although reasons for NOR amplification or ectopic location in the epidermal carcinoma A-431 cell line are not clear yet, our data suggest that these phenomena play a supporting role with regard to other amplified genes. Thus, the A-431 cell line would be an appropriate model to study the different mechanisms involved in human tumorigenesis.
Departamento de Genética, Instituto de Investigaciones Hematológicas "Mariano R. Castex," Academia Nacional de Medicina, Pacheco de Melo 3081, Buenos Aires 1425, Argentina. epedrazzini@hotmail.com
Estela
E
Pedrazzini
Nikolai
N
Mamaev
Tatyana
T
Yakovleva
Tatyana
T
Sukhikh
Marta
M
Salido
Francesc
F
Solé
Esther
E
Prat
Jordi
J
Camps
Rosa
R
Miró
Irma
I
Slavutsky
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms / Q000235:genetics*
D005819:Genetic Markers