Specific chromosomal aberrations in mouse lung adenocarcinoma cell lines detected by spectral karyotyping: a comparison with human lung adenocarcinoma.
Although adenocarcinoma is rapidly becoming the most common form of lung cancer in the United States, the difficulty in obtaining lung cancer families and representative samples of the various stages of adenocarcinoma progression has led to intense study of mouse models. As a powerful approach to delineating molecular changes, we have analyzed 15 early-passage mouse cell lines by spectral karyotyping. Entire copies of chromosomes 1, 2, 6, 12, 15, and 19 were gained, and entire copies of chromosomes 4, 7, 8, and 14 were lost. Significant gains of portions of chromosome 1 (93% of the tumor cell lines analyzed), chromosome 2 (53%), chromosome 6 (73%), chromosome 7 (80%), chromosome 12 (47%), and chromosome 15 (73%) and partial loss of chromosome 4 (87%), chromosome 7 (80%), chromosome 8 (53%), chromosome 10 (33%), and chromosome 14 (33%) were observed. Recurrent translocations included 10:del(10)(A1::C1), t(4;8)(C4;A1), and der (1;12)(C2;C2). The minimal regions of chromosomal alteration, 1G1, 2F1, 4C4, 6D, 7F1, 8B3, and 12C2, contain putative susceptibility genes for mouse lung adenocarcinoma. Chromosomal regions containing susceptibility genes linked to tumor size were frequently amplified, whereas regions with susceptibility loci linked to tumor multiplicity were deleted. Similar linkage groups are altered in human lung adenocarcinoma, implying that the mouse is a valid genetic model for the study of human lung adenocarcinoma susceptibility.
Sargent
Linda M
LM
National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Toxicology and Molecular Biology Branch, Genetic Susceptibility Team, Morgantown, West Virginia 26505, USA. Lsargent@cdc.gov
Senft
Jamie R
JR
Lowry
David T
DT
Jefferson
Amy M
AM
Tyson
Frederick L
FL
Malkinson
Alvin M
AM
Coleman
Allen E
AE
Reynolds
Steven H
SH
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D002869:Chromosome Aberrations; D005784:Gene Amplification; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D007621:Karyotyping; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D013045:Species Specificity; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured