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DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells

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Title DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells
 
Creator Gandhi, M
Dillon, L W
Pramanik, Sreemanta
Nikiforov, Y E
Wang, Y-H
 
Subject Biochemistry
 
Description Human chromosomal fragile sites are regions of the
genome that are prone to DNA breakage, and are
classified as common or rare, depending on their frequency
in the population. Common fragile sites frequently
coincide with the location of genes involved in carcinogenic
chromosomal translocations, suggesting their role in
cancer formation. However, there has been no direct
evidence linking breakage at fragile sites to the formation
of a cancer-specific translocation. Here, we studied the
involvement of fragile sites in the formation of RET/PTC
rearrangements, which are frequently found in papillary
thyroid carcinoma (PTC). These rearrangements are
commonly associated with radiation exposure; however,
most of the tumors found in adults are not linked to
radiation. In this study, we provide structural and
biochemical evidence that the RET, CCDC6 and NCOA4
genes participating in two major types of RET/PTC
rearrangements, are located in common fragile sites
FRA10C and FRA10G, and undergo DNA breakage
after exposure to fragile site-inducing chemicals. Moreover,
exposure of human thyroid cells to these chemicals
results in the formation of cancer-specific RET/PTC
rearrangements. These results provide the direct evidence
for the involvement of chromosomal fragile sites in the
generation of cancer-specific rearrangements in human cells
 
Publisher Nature Publishing Group
 
Date 2010
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://neeri.csircentral.net/856/1/SreemantaOncogene_2010.pdf
Gandhi, M and Dillon, L W and Pramanik, Sreemanta and Nikiforov, Y E and Wang, Y-H (2010) DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells. Oncogene, 29 (15). pp. 2272-2280. ISSN 0950-9232, ESSN: 1476-5594
 
Relation http://www.nature.com/onc/index.html
http://neeri.csircentral.net/856/