Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.
Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome.
Maser
Richard S
RS
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Choudhury
Bhudipa
B
Campbell
Peter J
PJ
Feng
Bin
B
Wong
Kwok-Kin
KK
Protopopov
Alexei
A
O'Neil
Jennifer
J
Gutierrez
Alejandro
A
Ivanova
Elena
E
Perna
Ilana
I
Lin
Eric
E
Mani
Vidya
V
Jiang
Shan
S
McNamara
Kate
K
Zaghlul
Sara
S
Edkins
Sarah
S
Stevens
Claire
C
Brennan
Cameron
C
Martin
Eric S
ES
Wiedemeyer
Ruprecht
R
Kabbarah
Omar
O
Nogueira
Cristina
C
Histen
Gavin
G
Aster
Jon
J
Mansour
Marc
M
Duke
Veronique
V
Foroni
Letizia
L
Fielding
Adele K
AK
Goldstone
Anthony H
AH
Rowe
Jacob M
JM
Wang
Yaoqi A
YA
Look
A Thomas
AT
Stratton
Michael R
MR
Chin
Lynda
L
Futreal
P Andrew
PA
DePinho
Ronald A
RA
D000818:Animals; D043171:Chromosomal Instability / Q000235:genetics*; D002869:Chromosome Aberrations; D017124:Conserved Sequence / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D026801:Synteny / Q000235:genetics
D051059:PTEN Phosphohydrolase