Microarray-based comparative genomic hybridization of pheochromocytoma cell lines from neurofibromatosis knockout mice reveals genetic alterations similar to those in human pheochromocytomas.
Somatic genetic aberrations have been identified in both sporadic pheochromocytomas and those associated with familial tumor syndromes; however, individual variations between human tumors and the absence of in vitro human pheochromocytoma models hinder efforts to understand the roles of those aberrations in tumorigenesis. Pheochromocytomas occur frequently in neurofibromatosis knockout mice and we have recently developed cell lines from those tumors. The availability of multiple tumors from genetically identical animals provides a powerful tool for understanding the pathobiology of pheochromocytomas. For the present investigation, we performed a genomic scanning analysis of four mouse pheochromocytoma cell lines by standard cytogenetics and microarray-based comparative genomic hybridization in order to identify genetic common denominators. All of the lines showed losses of most or all of chromosome 9; three lines lost most or all of chromosome 4. Mouse chromosome 4 is homologous to human chromosome 1p, which is the most frequent deletion in human pheochromocytomas. Mouse chromosome 9 shows large areas of homology to human 3p, 3q, and 11q, which are also frequently deleted. These comparisons suggest that genetic mechanisms in the genesis of pheochromocytomas may be similar across species. Additional changes that may be specific to this model included complete or partial gains of chromosome 12 as seen in 3 of the 4 lines analyzed by array CGH.
Powers
James F
JF
Department of Pathology, Tufts-New England Medical Center, Boston, MA 02111, USA. jpowers1@tufts-nemc.org
Tischler
Arthur S
AS
Mohammed
Mansoor
M
Naeem
Rizwann
R
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D017253:Neurofibromatoses / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000379:methods; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology