Chromosomal Variations Within Aneuploid Cancer Lines

Abstract

S U M M A R Y Aneuploid cancers exhibit a wide spectrum of clinical aggressiveness, possibly because of varying chromosome compositions. To test this, karyotypes from the diploid CCD-34Lu fibroblast and the aneuploid A549 and SUIT-2 cancer lines underwent fluorescence in situ hybridization (FISH) and DAPI counterstaining. The number of DAPI-stained and FISH-identified chromosomes, 1-22, X,Y, as well as structural abnormalities, were counted and compared using the 2 , Mann-Whitney rank sum test and the Levene's equality of variance. Virtually all of the evaluable diploid CCD-34Lu karyotypes had 46 chromosomes with two normal-appearing homologues. The aneuploid chromosome numbers per karyotype were highly variable, averaging 62 and 72 for the A549 and SUIT-2 lines, respectively. However, the A549 chromosome numbers were more narrowly distributed than the SUIT-2 karyotype chromosome numbers. Furthermore, 25% of the A549 chromosomes had structural abnormalities compared to only 7% of the SUIT-2 chromosomes. The chromosomal compositions of the aneuploid A549 and SUIT-2 cancer lines are widely divergent, suggesting that diverse genetic alterations, rather than chance, may govern the chromosome makeups of aneuploid cancers.

A model for genetic complementation controlling the chromosomal abnormalities and loss of heterozygosity formation in cancer

“…1 ) for each cell line are listed in Table 2 . An excellent correspondence was found between these results and three of four previous studies of these cell lines (Diserens et al, 1981;Melcher et al, 2002;Isaka et al, 2003;Cottier et al, 2004): The modal chromosome number of the A549 cell line in this and previous studies was 63 ( Table 2 , Isaka et al, 2003;Cottier et al, 2004). Five of the A549 marker chromosomes in this study ( Table 2 ) were previously identified (Cottier et al, 2004): M1 = der(3)t(3;20), M2 = der(6)t(6;1), M4 = der(19)t(15;19), M5 = +der(19)t(15;19), and M6 = del(2).…”

“…The SUIT-2 cell line (derived from pancreatic adenocarcinoma, male) was propagated as previously described (Isaka et al, 2003). Specifically, cells were grown as a monolayer in appropriate media: DMEM (A549 and LN-18), Ham's F12K (LoVo) and McCoy's (SUIT-2) supplemented with L-glutamine, 10% FBS (Invitrogen Corporation, Carlsbad, CA), and sodium bicarbonate (Amersham Life Sciences; Arlington Heights, IL) (Nestor et al, 2001).…”

5-Bromo-2-deoxyuridine activates DNA damage signalling responses and induces a senescence-like phenotype in p16-null lung cancer cells

“…These adenocarcinoma-derived cells contain wild-type p53 and pRb but do not express p16, a protein usually required for senescence [34]. The cell line is also aneuploid and contains chromosomal abnormalities [35], and heterogenous subpopulations [36]. We report that the DNA damage response to BrdU in these cells involves the activation of Chk1, Chk2 and p53.…”

Characterization of Two Human Lung Adenocarcinoma Cell Lines by Reciprocal Chromosome Painting

“…The karyotype of A549 cell line had been analyzed by M-FISH (Park et al, 2001;Isaka et al, 2003;Cottier et al, 2004;Shen et al, 2008). Compared previous reported A549 karyotype, some differences were found.…”

“…Like GLC-82 cell line, A549 cell line also belongs to lung adenocarcinoma cell line, and has been widely used in studies of cell cycle, apoptosis and adhesion mechanisms in cancer cells (Cottier et al, 2004). The karyotype of A549 cell line was investigated by M-FISH and CGH (Park et al, 2001;Isaka et al, 2003;Cottier et al, 2004;Shen et al, 2008). But the flow-sorting of aberrant chromosomes in A549 has not been reported, nor has the reverse chromosome painting.…”