由 sufang 在 二, 07/29/2014 – 23:14 發表 Pre-published Field Effect NOTCH Oral Cancer
重要文獻:
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J Pathol. 2014 Jul 21. doi: 10.1002/path.4409. [Epub ahead of print]
Mutation, clonal fitness and field change in epithelial carcinogenesis. (pdf 4133)
Frede J1, Adams DJ, Jones PH.
Author information
Abstract
Developments in lineage tracing in mouse models have revealed how stem cells maintain normal squamous and glandular epithelia. Here we review recent quantitative studies tracing the fate of individual mutant stem cells which have uncovered how common oncogenic mutations alter cell behaviour, creating clones with a growth advantage that may persist long term. In the intestine this occurs by a mutant clone colonizing an entire crypt, whilst in the squamous oesophagus blocking differentiation creates clones that expand to colonize large areas of epithelium, a phenomenon known as field change. We consider the implications of these findings for early cancer evolution and the cancer stem cell hypothesis, and the prospects of targeted cancer prevention by purging mutant clones from normal appearing epithelia.
#1由 sufang 在 六, 08/02/2014 – 21:58 發表。
Activation of the NOTCH pathway in head and neck cancer
Cancer Res. 2014 Feb 15;74(4):1091-104. doi: 10.1158/0008-5472.CAN-13-1259. Epub 2013 Dec 18.
Activation of the NOTCH pathway in head and neck cancer. (PubMed Link)
Sun W1, Gaykalova DA, Ochs MF, Mambo E, Arnaoutakis D, Liu Y, Loyo M, Agrawal N, Howard J, Li R, Ahn S, Fertig E, Sidransky D, Houghton J, Buddavarapu K, Sanford T, Choudhary A, Darden W, Adai A, Latham G, Bishop J, Sharma R, Westra WH, Hennessey P, Chung CH, Califano JA.
Abstract
NOTCH1 mutations have been reported to occur in 10% to 15% of head and neck squamous cell carcinomas (HNSCC).
NOTCH signaling in a cohort of 44 HNSCC tumors and 25 normal mucosal samples through a set of expression, copy number, methylation, and mutation analyses.
Copy number increases were identified in NOTCH pathway genes, including the NOTCH ligand JAG1 and JAG2 and receptor NOTCH3.
Analysis of individual pathway-related genes revealed overexpression of ligands JAG1 In 32% of the HNSCC examined, activation of the downstream NOTCH effectors HES1/HEY1 was documented.
Our results revealed a bimodal pattern of NOTCH pathway alterations in HNSCC, with a smaller subset exhibiting inactivating NOTCH1 receptor mutations but a larger subset exhibiting other NOTCH1 pathway alterations, including increases in expression or gene copy number of the receptor or ligands as well as downstream pathway activation.
Our results imply that therapies that target the NOTCH pathway may be more widely suitable for HNSCC treatment than appreciated currently. PMID: 24351288