DNA copy number evolution in 19 Drosophila cell lines

Friday, November 08, 2013 — Poster Session III
10:00 a.m. – 12:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NIDDK	GEN-20

Authors

H. Lee
C.J. McManus
D. Cho
M. Eaton
F. Renda
M. Patrizia-Somma
L. Cherbas
G. May
S. Powell
D. Zhang
L. Zhan
A. Resch
J. Andrews
S.E. Celniker
P. Cherbas
T.M. Przytycka
M. Gatti
B. Oliver
B. Graveley
D. MacAlpine

Abstract

Aneuploidy is often deleterious at the organismal level, but is common in immortalized cell lines and tumors, where it may be an advantage to cells. We resequenced 19 Drosophila cell lines to explore biological consequences of aneuploidy. Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways. This supports the gene balance hypothesis of aneuploidy. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and bantam, encoding an anti-apoptosis miRNA. Third, we found that while copy number segments of two highly aneuploid cell lines differed, proto-oncogenes were over- represented in one (S2-DRSC), and tumor suppressor genes were under-represented in the other (Kc167). Our study illustrates how changes of genome structure may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis.