Genomic characterization of gene copy-number aberrations in endometrial carcinoma cell lines derived from endometrioid-type endometrial adenocarcinoma

Abstract

Endometrial carcinoma is one of the most common cancers in women. A limited number of endometrial carcinoma cell lines are available for studies of signal transduction pathways and experimental therapeutics in vitro. However, these cell lines have not been comprehensively characterized. In this study, we used genome-wide microarray-based comparative genomic hybridization (aCGH) technology to characterize five of the more commonly used endometrial cancer cell lines. We detected DNA copy-number gains in chromosomal regions 2q, 3p, 3q, 5q, 7p, 17q, and 19q in all five cell lines. Other common sites of copy-number gains, which were detected in four of five cell lines, included segments of chromosomes 1, 6, 8, 9, 11, 12, and 16. In all five cell lines, we found DNA copy-number losses in regions 3p, 10p, 10q, 11q, 11p, 14q, 15q, 18p, and 21q. Other common sites of genetic aberrations included segments of chromosomes 1, 2, 4, 5, 6, 16, 20, and 22. The genes involved in the copy-number alterations included the oncogenes PIK3CA (3q26.3), K-ras (12p12.1), R-ras (19q13.3-qter), Raf-1 (3p25), EGFR (7p12), Akt1 (14q32.32), and Akt2 (19q13.1-q13.2). A pathway analysis showed that genes in the PI3K and Wnt pathways are commonly affected. Our characterization of genomic alterations in these five commonly used endometrial cancer cell lines provides valuable genomic information for research that focuses on these key oncogenic pathways in endometrial cancer.

Figure 1

Array-based comparative genomic hybridization profile of five endometrial carcinoma cell lines. The chromosomes are aligned sequentially on the x-axis and are demarcated by the vertical lines. The y-axis shows chromosomal regions of either gain (positive numbers) or loss (negative numbers) relative to normal control genomic DNA isolated from healthy subjects.

Figure 2

Frequency analysis of DNA copy–number alterations in all five endometrial carcinoma cell lines by array-based comparative genomic hybridization. The y-axis shows the recurrence of gains or losses for each measured sequence, which are aligned evenly in chromosomal order on the x-axis. The horizontal dashed line indicates the threshold for a significant number of aberrations. Red lines indicate a significant frequency of DNA copy–number gains and green lines indicate a significant frequency of DNA copy–number losses. The gray color represents nonsignificant recurrence of aberrations. Borders between chromosomes are indicated by vertical bars, and those between the short arm and long arm of a chromosome are indicated by vertical dashed bars.