Centrosomal dysregulation in human metastatic melanoma cell lines.
Correct partitioning of the replicated genome during mitosis is orchestrated by centrosomes, and chromosomal instability is a commonly reported feature of human cancer. Melanomas are notorious for their genetic instability and rapid clonal evolution that may be manifested as aggressive growth and facile generation of therapy-resistant variants. We characterized the centrosomal status, ploidy, and gene status (TP53, CDKN2A/B, BRAF, and NRAS) of 15 human metastatic melanoma cell lines. Cells were labelled for pericentrin (a centrosomal marker), DNA and α-tubulin, and scored for centrosome morphology, supernumerary centrosomes, and mitotic symmetry. The incidence of supernumerary centrosomes correlated with that of gross centrosomal abnormalities (r = 0.90), mitotic asymmetry (r = 0.90), and, surprisingly, increased content of G/M cells (r = 0.79). Centrosomal numerical dysregulation, observed in all cell lines, was found not to be specifically related to the status of any of the characterized gene mutations that were found in 13/15 cell lines. We conclude that centrosomal dysregulation may arise from multiple mechanisms and may drive the generation of genetic and phenotypic diversity in melanoma.
Auckland Cancer Society Research Centre, The University of Auckland, New Zealand.
Geoffrey A
GA
Charters
Clare J
CJ
Stones
Andrew N
AN
Shelling
Bruce C
BC
Baguley
Graeme J
GJ
Finlay
D045744:Cell Line, Tumor; D018385:Centrosome / Q000502:physiology* / Q000648:ultrastructure; D043171:Chromosomal Instability; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure; D011003:Ploidies