NDLI: Pretumor Progression

Content Provider	PubMed Central
Author	Calabrese, Peter Tavaré, Simon Shibata, Darryl
Copyright Year	2004
Abstract	Multistep carcinogenesis through sequential cycles of mutation and clonal succession is usually described as tumor progression, or the clonal evolution of tumor cell populations. However, many mutations found in cancers are also compatible with normal appearing phenotypes and therefore genetic progression may precede tumor progression. To better characterize such pretumor progression (mutations in the absence of visible phenotypic changes), a quantitative model was developed that postulates most oncogenic cancer mutations first accumulate in normal appearing colon crypt niche stem cells. Each crypt contains multiple stem cells, and random niche stem cell loss with replacement eventually leads to the loss of all stem cell lineages except one. This niche succession or crypt clonal evolution is similar to the clonal succession of tumor progression except it does not require selection or change visible phenotype. Mutations may sequentially accumulate during stem cell clonal evolution either through drift (passenger mutations) or selection. To determine the feasibility of pretumor progression, mutation rates sufficient to recreate the epidemiology of colorectal cancer were estimated. Pretumor progression may completely substitute for visible tumor progression because it is theoretically possible for all cancer mutations to first accumulate in normal appearing colon with normal replication fidelity. Elevated mutation rates or tumorigenesis may be unnecessary for early progression.
Related Links	http://dx.doi.org/10.1016/s0002-9440(10)63220-8
Ending Page	1346
Page Count	10
Starting Page	1337
File Format	PDF
ISSN	00029440
e-ISSN	15252191
Journal	The American Journal of Pathology
Issue Number	4
Volume Number	164
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	2004-04-01
Access Restriction	Open
Rights Holder	American Society for Investigative Pathology
Subject Keyword	Pathology and Forensic Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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