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Histological and molecular evaluation of patient-derived colorectal cancer explants.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (6), pp. e38422. Date of Electronic Publication: 2012 Jun 04. - Publication Year :
- 2012
-
Abstract
- Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.
- Subjects :
- Animals
CDX2 Transcription Factor
Cell Nucleus metabolism
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Mice
Mutation genetics
Oncogenes genetics
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins p21(ras)
ras Proteins genetics
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Xenograft Model Antitumor Assays
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22675560
- Full Text :
- https://doi.org/10.1371/journal.pone.0038422