Correlation Between Mutation in P53, p53 Expression, Cytogenetics, Histologic Type, and Survival in Patients With B-Cell Non-Hodgkin's Lymphoma

作者: Prasad R.K. Koduru , Karthik Raju , Veena Vadmal , Geetha Menezes , Shefali Shah

DOI: 10.1182/BLOOD.V90.10.4078

关键词:

摘要: In the biology of a cell, central role p53 in controlling functions such as G1/S transition (check point) and DNA damage repair, trigger apoptosis, is well established. Somatic mutations or other changes P53 have been reported numerous tumor types, some these, they are associated with poor prognosis. this study, we examined 237 cytogenetically characterized B-cell non-Hodgkin's lymphomas (B-NHLs) for somatic by Southern blot analysis, single-strand conformation polymorphism analysis (SSCP) exon 5 through 9, direct sequencing SSCP variants to determine frequency types their clinical significance. portion these (173 tumors), also studied expression immunostaining. On blots, no gross change was identified mutation 9. exons 8, 27 different were 25 patients (23 single-base substitutions, 3 deletions, 1 duplication). Mutations tumors (10.5%), which included 45 small lymphocytic (SLLs), 2 38 follicular cleaved-cell (FSCCs), 35 mixed large-cell (FMxs), 4 (FLCs), 14 diffuse (DSCCs), 17 small- (DMxs), 16 84 (DLCCs); difference between histologic groups significant (P < .01). Among mantle-cell lymphoma (MC) patients, 10 had mutations. specimens obtained at diagnosis. Mutation type transversion occurred relative 2:1. Thirty percent CpG dinucleotide sequences codon arginine most frequently affected. Nineteen 99 complex cytogenetic abnormalities, but none 69 simple .001). Similarly, 11 an abnormality 17p 8 143 apparently normal .0001). Positive correlations found .001), missense .005), abnormalities .05). Twenty-two 49 without died .05), there median survival. 21 26 positive died, whereas only 24 p53-negative on-study .01) positively fatal outcome. These findings indicate that B-NHL, present diagnostic all higher DLC MC tumors. and/or has negative influence on survival, therefore can serve prognostic indicators. Immunostaining effective way screen

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