Carcinogenesis is thought to originate from a single cell which accumulates a series of well-defined, albeit randomly obtained, genetic mutations, leading to carcinogenic transformation. Despite the inroads into elucidating the carcinogenesis process, there still remain gaps in our understanding of how mutations drive cell transformation and subsequent cancer progression. Although gene mutations clearly contribute to cancer, no single mutated gene or combination of mutated genes occur in all or even the majority of cancers. Moreover, as Vogelstein and Kinzler {Nature Rev Cancer 2004) point out, it is not gene mutations, but primarily chromosome-level aberrations that cells exhibit following transformation to the cancer state. Although it has long been assumed that cancers arise from mutated differentiated cells, mutated stem cells are now also considered candidate cancer precursors due to their self-renewal and differentiation capacity. Although genomic instability is ubiquitous across malignant cancers, its mechanistic underpinnings remain unclear. Inhibition of stability genes, alterations in mitosis genes, aberrant centrosomes, aneuploidy, telomere dysregulations and, for virus-linked cancers, virus-induced fusion of genetically-mutated cells, are all candidate causes of the instability. Given that gene mutations and particularly chromosome aberrations decrease the fitness of a cell, how is it that cancer cell populations are able to sustain and proliferate in the face of the high degree of chromosomal damage per cell? If the answer lies in the existence of cancer stem cells, one needs to ask how this privileged cell compartment is itself exempt from the deleterious effects of chromosomal damage.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA149233-04
Application #
8536740
Study Section
Special Emphasis Panel (ZCA1-SRLB-C)
Project Start
Project End
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$122,748
Indirect Cost
Name
Genesys Research Institute, Inc.
Department
Type
DUNS #
965467512
City
Boston
State
MA
Country
United States
Zip Code
02135
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