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Genetic alterations of RD INK4/ARF enhancer in human cancer cells
Author(s) -
Li Junan,
Knobloch Thomas J.,
Poi Ming J.,
Zhang Zhaoxia,
Davis Andrew T.,
Muscarella Peter,
Weghorst Christopher M.
Publication year - 2014
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.21965
Subject(s) - biology , enhancer , carcinogenesis , locus (genetics) , cancer research , cancer , gene , tumor suppressor gene , cancer cell , microbiology and biotechnology , genetics , transcription factor
Recent identification of an enhancer element, RD INK4/ARF (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15 INK4B ( p15 ), p14 ARF , and p16 INK4A ( p16 ) tumor suppressor genes. While genetic inactivation of p15 , p14 ARF , and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15 , p14 ARF , and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using real‐time PCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15 , p14 ARF , and p16 . Furthermore, the status of RD was poorly associated with the expression of p15 , p14 ARF , and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored. © 2012 Wiley Periodicals, Inc.