Premium
Oncogenic aberrations in the p53 pathway are associated with a high S phase fraction and poor patient survival in b‐cell non‐Hodgkin's lymphoma
Author(s) -
Stokke Trond,
Galteland Eivind,
Holte Harald,
Smedshammer Lars,
Suo Zhenhe,
Smeland Erlend B.,
BørresenDale AnneLise,
DeAngelis Paula,
Steen Harald B.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000720)89:4<313::aid-ijc1>3.0.co;2-d
Subject(s) - lymphoma , missense mutation , biology , immunohistochemistry , apoptosis , exon , fluorescence in situ hybridization , allele , cancer research , cancer , microbiology and biotechnology , survival analysis , pathology , mutation , genetics , medicine , gene , immunology , chromosome
The implications of aberrations in the p53 pathway for induction of apoptosis and regulation of S phase entry, and for patient survival, were investigated in 83 B‐cell Non‐Hodgkin's lymphomas. Eight cases had missense mutations in exons 5, 7, 8 and 9 as revealed by constant denaturant gel electrophoresis and sequencing. Fifteen cases had lost 1 TP53 allele as revealed by fluorescent in situ hybridization and comparative genomic hybridization. Ten cases expressed high levels of p53 as assessed by immunoblotting and immunohistochemistry. S phase fractions were higher, apoptotic fractions were the same and survival times were shorter in all aberration groups compared with the cases with no TP53 /p53 aberrations. Since many tumors had more than one TP53 /p53 aberration, the tumors were divided into groups with the following characteristics: no TP53 /p53 aberrations; loss of one TP53 allele only (9 cases), TP53 point mutation (8 cases), high‐level p53 expression and no TP53 mutation (3 cases). Tumors from the 3 latter groups had higher median S phase fractions (5%, 7.6%, and 5%, respectively, p <0.02) than the cases without any aberrations (1.1%), and survival time for these patients was much shorter (relative risks of 5.9, 8.9, and 6.6, respectively, p <0.003). Apoptotic fractions were similar in all these groups ( p =0.09). Multivariate analysis showed that the presence of TP53 /p53 aberrations is a strong and independent prognostic parameter in B‐cell Non‐Hodgkin's lymphoma. Int. J. Cancer 89:313–324, 2000. © 2000 Wiley‐Liss, Inc.