Premium
TP 53 pathway analysis in paediatric B urkitt lymphoma reveals increased MDM 4 expression as the only TP 53 pathway abnormality detected in a subset of cases
Author(s) -
Leventaki Vasiliki,
Rodic Vladimir,
Tripp Sheryl R.,
Bayerl Michael G.,
Perkins Sherrie L.,
Barnette Phillip,
Schiffman Joshua D.,
Miles Rodney R.
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09243.x
Subject(s) - lymphoma , chemistry , microbiology and biotechnology , medicine , immunology , biology
Summary The TP 53 (p53) pathway can be inhibited by TP 53 mutation or deletion or by MDM 2 overexpression. Both occur in B urkitt lymphoma ( BL ), but many cases lack either abnormality. Expression patterns of the TP 53 inhibitor MDM 4 have not been reported in BL , and increased MDM 4 could deregulate the TP 53 pathway in cases without TP 53 or MDM 2 abnormalities. We investigated TP 53 pathway disruption in paediatric BL patient samples ( n = 30) by studying MDM 4, MDM 2, and CDKN 1 A (p21) protein and m RNA expression; TP 53 mutations; TP 53 protein expression; and gene copy number abnormalities. MDM 4 protein was expressed in 30/30 tumours, and MDM 2 protein was weakly expressed in 7/30 (23%). All cases were negative for CDKN 1 A protein, and CDKN 1 A m RNA levels were decreased. TP 53 mutations were detected in 5/28 (18%) cases and confirmed by sequencing. TP 53 protein was expressed in 15/30 (50%) cases, including 7/8 with TP 53 genetic alterations. MDM 2 protein and m RNA expression levels did not correlate with lack of TP 53 genetic changes or TP 53 protein expression; however, there was an inverse relationship between detectable TP 53 protein expression and MDM 4 copy number gains and m RNA expression. The TP 53 pathway is deregulated in paediatric BL cases, and increased MDM 4 expression may be the primary mechanism in some cases.