by
Karuna Mittal;
Da Hoon Choi;
Angela Ogden;
Shashi Donthamsetty;
Brian D. Melton;
Meenakshi V. Gupta;
Vaishali Pannu;
Guilherme Cantuaria;
Sooryanarayana Varambally;
Michelle Reid;
Kristin Jonsdottir;
Emiel A. M. Janssen;
Mohammad A. Aleskandarany;
Ian O. Ellis;
Emad A. Rakha;
Padmashree C. G. Rida;
Ritu Aneja
Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines. We find that mitoses are rare in patient tumors compared with xenografts and cell lines. Contrastingly, CA is more extensive in patient tumors and xenografts (∼35-50% cells) than cell lines (∼5-15%), although CA declines in patient-derived tumor cells over time. Intratumoral hypoxia may explain elevated CA in vivo because exposure of cultured cells to hypoxia or mimicking hypoxia pharmacologically or genetically increases CA, and HIF-1α and hypoxic gene signature expression correlate with CA and centrosomal gene signature expression in breast tumors. These results highlight the importance of utilizing low-passage-number patient-derived cell lines in studying CA to more faithfully recapitulate in vivo cellular phenotypes.