Showing papers by "Eric R. Fearon published in 2016"
TL;DR: The occurrence of significant intra-tumor heterogeneity in rectal cancers involving variations in localized somatic mutations and copy number abnormalities may allow selected tumors to have a genetic reservoir to draw from in their evolutionary response to therapy and other challenges.
62 citations
TL;DR: The utility of Ovgp1‐iCreERT2 mice for manipulating genes of interest specifically in the oviductal epithelium is demonstrated, and it is established that the cell of origin is an important consideration in mouse ovarian cancer GEMMs.
Abstract: Endometrioid carcinoma (EC) is a relatively indolent ovarian carcinoma subtype that is nonetheless deadly if detected late. Existing genetically engineered mouse models (GEMMs) of the disease, based on transformation of the ovarian surface epithelium (OSE), take advantage of known ovarian EC driver gene lesions, but do not fully recapitulate the disease features seen in patients. An EC model in which the Apc and Pten tumour suppressor genes are conditionally deleted in murine OSE yields tumours that are biologically more aggressive and significantly less differentiated than human ECs. Importantly, OSE is not currently thought to be the tissue of origin of most ovarian cancers, including ECs, suggesting that tumour initiation in Mullerian epithelium may produce tumours that more closely resemble their human tumour counterparts. We have developed Ovgp1-iCreERT2 mice in which the Ovgp1 promoter controls expression of tamoxifen (TAM)-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human Fallopian tube epithelium. Ovgp1-iCreERT2 ;Apcfl/fl ;Ptenfl/fl mice treated with TAM or injected with adenovirus expressing Cre into the ovarian bursa uniformly develop oviductal or ovarian ECs, respectively. On the basis of their morphology and global gene expression profiles, the oviduct-derived tumours more closely resemble human ovarian ECs than do OSE-derived tumours. Furthermore, mice with oviductal tumours survive much longer than their counterparts with ovarian tumours. The slow progression and late metastasis of oviductal tumours resembles the relatively indolent behaviour characteristic of so-called Type I ovarian carcinomas in humans, for which EC is a prototype. Our studies demonstrate the utility of Ovgp1-iCreERT2 mice for manipulating genes of interest specifically in the oviductal epithelium, and establish that the cell of origin is an important consideration in mouse ovarian cancer GEMMs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
57 citations
TL;DR: A subgroup of stage II colon cancer patients that might benefit from adjuvant chemotherapy based on lack of CDX2 expression in their cancer stem cells is identified.
5 citations
5 citations