scholarly journals The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations

Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 3151-3156 ◽  
Author(s):  
R Villuendas ◽  
MA Piris ◽  
P Algara ◽  
M Sanchez-Beato ◽  
L Sanchez-Verde ◽  
...  
Keyword(s):  
P53 Protein ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
High Grade ◽  
P53 Mutations ◽  
P53 Gene Mutations ◽  
Hodgkin's Lymphomas

p53 overexpression has been found to be a fairly common feature in high grade lymphomas in the majority of tumoral cells. The results vary from series to series, from 25% to 33% of cases. To assess whether immunohistochemical positivity for p53 correlated with the presence of structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with high and low p53 values was amplified and sequenced to determine the existence of point mutations in the highly conserved regions of the p53 gene. In the group of 8 cases containing high levels of protein, 3 cases showed missense point mutations at the codons mapping between exons 5 through 8. Of the 8 cases of tumors containing undetectable or low levels of p53 protein, 1 case presented a nonsense point mutation giving a stop codon. No missense mutations were detected in this group. The finding of p53 mutations in 4 of 16 cases confirms the presence of p53 gene mutations in high grade lymphomas distributed over different histologic groups. These include Burkitt's lymphoma, together with centroblastic, immunoblastic, and large cell lymphoma of mucosa origin. Nevertheless, the absence of mutations in 5 of the 8 cases that overexpressed p53 suggests that the nuclear or cytoplasmic stabilization of p53 protein could also depend on other factors. The absence of detectable levels of p53 protein cannot discount the existence of p53 mutations, as is shown by a case of Burkitt's lymphoma in which a nonsense mutation was detected. The impact of this range of p53 alterations on clinical course and treatment response of the patients deserves to be explored, in an attempt to differentiate the specific consequences of each one.

scholarly journals The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations

Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 3151-3156 ◽  
Author(s):  
R Villuendas ◽  
MA Piris ◽  
P Algara ◽  
M Sanchez-Beato ◽  
L Sanchez-Verde ◽  
...  
Keyword(s):  
P53 Protein ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
High Grade ◽  
P53 Mutations ◽  
P53 Gene Mutations ◽  
Hodgkin's Lymphomas

Abstract p53 overexpression has been found to be a fairly common feature in high grade lymphomas in the majority of tumoral cells. The results vary from series to series, from 25% to 33% of cases. To assess whether immunohistochemical positivity for p53 correlated with the presence of structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with high and low p53 values was amplified and sequenced to determine the existence of point mutations in the highly conserved regions of the p53 gene. In the group of 8 cases containing high levels of protein, 3 cases showed missense point mutations at the codons mapping between exons 5 through 8. Of the 8 cases of tumors containing undetectable or low levels of p53 protein, 1 case presented a nonsense point mutation giving a stop codon. No missense mutations were detected in this group. The finding of p53 mutations in 4 of 16 cases confirms the presence of p53 gene mutations in high grade lymphomas distributed over different histologic groups. These include Burkitt's lymphoma, together with centroblastic, immunoblastic, and large cell lymphoma of mucosa origin. Nevertheless, the absence of mutations in 5 of the 8 cases that overexpressed p53 suggests that the nuclear or cytoplasmic stabilization of p53 protein could also depend on other factors. The absence of detectable levels of p53 protein cannot discount the existence of p53 mutations, as is shown by a case of Burkitt's lymphoma in which a nonsense mutation was detected. The impact of this range of p53 alterations on clinical course and treatment response of the patients deserves to be explored, in an attempt to differentiate the specific consequences of each one.

Increased p53 Protein Does Not Correlate to p53 Gene Mutations in Microdissected Human Testicular Germ Cell Tumors

1995 ◽  
Vol 154 (2) ◽  
pp. 617-621 ◽  
Author(s):  
Noah S. Schenkman ◽  
Isabell A. Sesterhenn ◽  
Lucille Washington ◽  
Yue Ao Tong ◽  
Christopher M. Weghorst ◽  
...  
Keyword(s):  
Germ Cell ◽  
P53 Protein ◽  
Germ Cell Tumors ◽  
Gene Mutations ◽  
P53 Gene ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
P53 Gene Mutations

Increased p53 Protein Does Not Correlate to p53 Gene Mutations in Microdissected Human Testicular Germ Cell Tumors

1995 ◽  
pp. 617-621 ◽  
Author(s):  
Noah S. Schenkman ◽  
Isabell A. Sesterhenn ◽  
Lucille Washington ◽  
Yue Ao Tong ◽  
Christopher M. Weghorst ◽  
...  
Keyword(s):  
Germ Cell ◽  
P53 Protein ◽  
Germ Cell Tumors ◽  
Gene Mutations ◽  
P53 Gene ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
P53 Gene Mutations

scholarly journals Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS- derived leukemia

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 3022-3026 ◽  
Author(s):  
K Sugimoto ◽  
N Hirano ◽  
H Toyoshima ◽  
S Chiba ◽  
H Mano ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
P53 Gene Mutation ◽  
Ras Gene ◽  
P53 Gene Mutations

The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas. We present here evidence for the possible involvement of p53 gene mutations in the myelodysplastic syndrome (MDS), although the incidence is relatively low. Forty-four patients with MDS and six patients with overt leukemias that developed from MDS were studied for p53 gene alterations using reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Three patients with MDS (2 RAEB and 1 RAEB in T) had missense point mutations in the conserved regions of the p53 coding sequence. Furthermore, expression of the wild-type p53 mRNA was not detected in these three patients. The probable absence of normal p53 function in the three cases studied here suggests that alterations in the p53 gene may occasionally play a role in MDS. These three MDS patients with p53 gene mutations and an MDS-derived erythroleukemia cell line that we had previously reported to carry a p53 gene mutation showed no N-ras gene mutations, suggesting heterogeneity in the oncogenic mechanism of MDS.

scholarly journals p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression

Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3452-3459 ◽  
Author(s):  
S el Rouby ◽  
A Thomas ◽  
D Costin ◽  
CR Rosenberg ◽  
M Potmesil ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Gene Mutations ◽  
P53 Gene ◽  
Lymphocytic Leukemia ◽  
P53 Mutations ◽  
P53 Gene Mutation ◽  
P53 Gene Mutations ◽  
Cell Chronic Lymphocytic Leukemia

We studied 53 patients with B-cell chronic lymphocytic leukemia (B-CLL) and found mutations of the p53 gene in 15%. Patients with p53 gene mutations were found to have an aggressive form of B-CLL disease characterized by advanced Rai stage, rapid lymphocyte doubling time (LDT), and resistance to chemotherapy. While 27 of 29 treated patients (93%) without p53 mutations achieved a partial remission, only one of seven treated patients (14%) with p53 mutations achieved a partial remission (P = .00009). Adjusting for prognostic factors (age, sex, race, and Rai stage), patients with p53 gene mutations had a 13-fold greater risk of death than patients without p53 mutations (P = .013). In addition to examining the clinical relevance of p53 gene mutations in B-CLL, we investigated the possible role of p53 gene regulation in the expression of the multidrug resistance genes MDR1 and MDR3. We quantitated MDR1 and MDR3 mRNA expression by reverse transcription- polymerase chain reaction (RT-PCR). Expression of both the MDR1 and MDR3 genes was independent of p53 gene mutation or prior drug treatment, and did not predict for clinical response. Our findings indicate that p53 gene mutations in B-CLL are associated with a poor clinical outcome and may be a prognostic indicator for drug resistance.

scholarly journals Molecular analysis of cutaneous B- and T-cell lymphomas

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3160-3172 ◽  
Author(s):  
A Neri ◽  
NS Fracchiolla ◽  
E Roscetti ◽  
S Garatti ◽  
D Trecca ◽  
...  
Keyword(s):  
T Cell ◽  
Southern Blot ◽  
Gene Mutations ◽  
P53 Gene ◽  
Gene Deletions ◽  
T Cell Lymphomas ◽  
Cutaneous Lymphomas ◽  
P53 Gene Mutations ◽  
Hodgkin's Lymphomas ◽  
T Cell Malignancies

Abstract Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.

scholarly journals MDM2 overexpression does not account for stabilization of wild-type p53 protein in non-Hodgkin's lymphomas

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3239-3246 ◽  
Author(s):  
R Maestro ◽  
A Gloghini ◽  
C Doglioni ◽  
D Gasparotto ◽  
T Vukosavljevic ◽  
...  
Keyword(s):  
P53 Protein ◽  
P53 Gene ◽  
Critical Ratio ◽  
Low Grade ◽  
High Grade ◽  
Protein Overexpression ◽  
Wild Type ◽  
Donor And Acceptor ◽  
Hodgkin's Lymphomas ◽  
Mdm2 Overexpression

p53 protein overexpression is a frequent finding in non-Hodgkin's lymphomas (NHL), being detected in over 25% of the cases. Moreover, some high-grade lymphomas and a large fraction of low-grade tumors show a pattern of scattered p53 accumulation in a limited percentage of neoplastic cells. In contrast, NHLs show a low frequency of p53 gene mutations. To investigate the molecular bases of p53 protein overexpression, a large series of NHLs was analyzed for p53 gene status. The analysis of the entire coding region of the gene (exons 2–11) and corresponding donor and acceptor splicing sites indicated that a significant proportion of p53-positive tumors overexpresses a wild-type form of p53 protein (wt-p53). To assess whether wt-p53 accumulation was related to the formation of inactive complexes with endogenous proteins, MDM2 oncogene expression and amplification were analyzed. MDM2 overexpression was detected only in one third of the wt-p53-positive cases, thus excluding that MDM2 accounts tout court for the accumulation of a normal p53 protein. However, the fact that MDM2 overexpression was detected in only the p53-positive cases and the observation that MDM2-positive cells were a subpopulation of p53-positive cells suggest a link between the two phenomena. In particular, our results indicate that the accumulation of a wt form of p53 protein could promote the overexpression of the MDM2 gene product. In addition, the prevalence of MDM2 positivity in intermediate/high-grade tumors together with the concordant expression of wt-p53 and MDM2 only in the high-grade component of a ‘composite’ lymphoma suggests that perturbation in the MDM2/p53 critical ratio could play a role in lymphoma progression.

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