| BELMONT, Peter J., Eva BUDINSKÁ, Ping JIANG, Mark J. SINNAMON, Erin COFFEE, Jatin ROPER, Tao XIE, Paul A. REJTO, Sahra DERKITS, Owen J. SANSOM, Mauro DELORENZI, Sabine TEJPAR, Kenneth E. HUNG and Eric S. MARTIN. Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease. Disease models & mechanisms. Cambridge: Company of Biologists Ltd., 2014, vol. 7, No 6, p. 613-623. ISSN 1754-8403. Available from: https://dx.doi.org/10.1242/dmm.013904. |
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@article{1184738,
author = {Belmont, Peter J. and Budinská, Eva and Jiang, Ping and Sinnamon, Mark J. and Coffee, Erin and Roper, Jatin and Xie, Tao and Rejto, Paul A. and Derkits, Sahra and Sansom, Owen J. and Delorenzi, Mauro and Tejpar, Sabine and Hung, Kenneth E. and Martin, Eric S.},
article_location = {Cambridge},
article_number = {6},
doi = {http://dx.doi.org/10.1242/dmm.013904},
keywords = {KRAS; BRAF; MAPK; Colorectal cancer; GEMM; Genomic signatures},
language = {eng},
issn = {1754-8403},
journal = {Disease models & mechanisms},
title = {Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease},
volume = {7},
year = {2014}
}
TY - JOUR
ID - 1184738
AU - Belmont, Peter J. - Budinská, Eva - Jiang, Ping - Sinnamon, Mark J. - Coffee, Erin - Roper, Jatin - Xie, Tao - Rejto, Paul A. - Derkits, Sahra - Sansom, Owen J. - Delorenzi, Mauro - Tejpar, Sabine - Hung, Kenneth E. - Martin, Eric S.
PY - 2014
TI - Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease
JF - Disease models & mechanisms
VL - 7
IS - 6
SP - 613-623
EP - 613-623
PB - Company of Biologists Ltd.
SN - 17548403
KW - KRAS
KW - BRAF
KW - MAPK
KW - Colorectal cancer
KW - GEMM
KW - Genomic signatures
N2 - Effective treatment options for advanced colorectal cancer (CRC) are limited, survival rates are poor and this disease continues to be a leading cause of cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a large subset of individuals with sporadic CRC typically harbor relatively few established ‘driver’ lesions. Here, we describe a collection of genetically engineered mouse models (GEMMs) of sporadic CRC that combine lesions frequently altered in human patients, including well-characterized tumor suppressors and activators of MAPK signaling. Primary tumors from these models were profiled, and individual GEMM tumors segregated into groups based on their genotypes. Unique allelic and genotypic expression signatures were generated from these GEMMs and applied to clinically annotated human CRC patient samples. We provide evidence that a Kras signature derived from these GEMMs is capable of distinguishing human tumors harboring KRAS mutation, and tracks with poor prognosis in two independent human patient cohorts. Furthermore, the analysis of a panel of human CRC cell lines suggests that high expression of the GEMM Kras signature correlates with sensitivity to targeted pathway inhibitors. Together, these findings implicate GEMMs as powerful preclinical tools with the capacity to recapitulate relevant human disease biology, and support the use of genetic signatures generated in these models to facilitate future drug discovery and validation efforts.
ER -
BELMONT, Peter J., Eva BUDINSKÁ, Ping JIANG, Mark J. SINNAMON, Erin COFFEE, Jatin ROPER, Tao XIE, Paul A. REJTO, Sahra DERKITS, Owen J. SANSOM, Mauro DELORENZI, Sabine TEJPAR, Kenneth E. HUNG and Eric S. MARTIN. Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease. \textit{Disease models \&{} mechanisms}. Cambridge: Company of Biologists Ltd., 2014, vol.~7, No~6, p.~613-623. ISSN~1754-8403. Available from: https://dx.doi.org/10.1242/dmm.013904.
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