Identification of alterations in DNA copy number in host stromal cells during tumor progression.
The interactions between cancer cells and the surrounding host stromal tissue play a critical role in tumor progression and metastasis, but the molecular nature of this relationship remains largely uncharacterized. Furthermore, although genetic changes of neoplastic cells in tumors contribute significantly to tumor progression, it is not known whether similar changes occur in the adjacent host stromal microenvironment and whether they contribute to or inhibit tumorigenesis. To address this question in an unbiased and genome-wide manner, we applied high-resolution DNA copy number analysis to murine stromal DNA isolated from human xenograft tumors that were formed in immunodeficient mice. We show that numerous amplifications and deletions are found within the host stromal microenvironment, suggesting that alterations in host DNA copy number can occur and may play a significant role in modifying tumor-stromal interactions.
Pelham
Robert J
RJ
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. rpelham@princeton.edu
Rodgers
Linda
L
Hall
Ira
I
Lucito
Robert
R
Nguyen
Ken C Q
KC
Navin
Nicholas
N
Hicks
James
J
Mu
David
D
Powers
Scott
S
Wigler
Michael
M
Botstein
David
D
D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D018628:Gene Dosage / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism
D004247:DNA