scholarly journals p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 128-135 ◽  
Author(s):  
A Neri ◽  
L Baldini ◽  
D Trecca ◽  
L Cro ◽  
E Polli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
P53 Mutation ◽  
Late Event ◽  
Multistep Process ◽  
P53 Gene Mutations

Abstract The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.

scholarly journals p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 128-135 ◽  
Author(s):  
A Neri ◽  
L Baldini ◽  
D Trecca ◽  
L Cro ◽  
E Polli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
P53 Mutation ◽  
Late Event ◽  
Multistep Process ◽  
P53 Gene Mutations

The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.

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 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

Abstract 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 mutations in multiple myeloma.

1997 ◽  
Vol 50 (1) ◽  
pp. 18-20 ◽  
Author(s):  
R G Owen ◽  
S A Davis ◽  
J Randerson ◽  
A C Rawstron ◽  
F Davies ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Gene Mutations ◽  
P53 Gene ◽  
P53 Gene Mutations

Rare occurrence of P53 gene mutations in multiple myeloma

1992 ◽  
Vol 81 (3) ◽  
pp. 440-443 ◽  
Author(s):  
Claude Preudhomme ◽  
Thierry Facon ◽  
Marc Zandecki ◽  
Mickael Vanrumbeke ◽  
Jean Luc Laï ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Gene Mutations ◽  
P53 Gene ◽  
Rare Occurrence ◽  
P53 Gene Mutations

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 p53 mutations are associated with histologic transformation of follicular lymphoma

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2289-2295 ◽  
Author(s):  
F Lo Coco ◽  
G Gaidano ◽  
DC Louie ◽  
K Offit ◽  
RS Chaganti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Low Grade ◽  
Diffuse Type ◽  
P53 Mutations ◽  
Clinical Progression ◽  
Hodgkin's Lymphomas

Abstract The majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.

scholarly journals P53 gene mutations in acute myeloid leukemia with 17p monosomy

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1652-1657 ◽  
Author(s):  
P Fenaux ◽  
P Jonveaux ◽  
I Quiquandon ◽  
JL Lai ◽  
JM Pignon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
Cytogenetic Abnormalities ◽  
P53 Gene Mutations ◽  
Acute Myeloid

Abstract We looked for mutations of exons 5 to 8 of the P53 gene in 10 patients with acute myeloid leukemia (AML) and 17p monosomy, and 36 patients with AML and no cytogenetic abnormalities of 17p. DNA was analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Four of the 10 patients with 17p monosomy showed point mutation, single-nucleotide deletion, or insertion in exons 7 or 8. By contrast, only 1 of the 36 patients with AML and no cytogenetic abnormalities of 17p showed a mutation of the P53 gene in exons 5 to 8 (P less than .01). These results suggest that alterations of the P53 gene may have a role in leukemogenesis in some cases of AML. The fact that P53 gene mutations occurred more often in patients with 17p monosomy seems to support the “recessive” model of tumor suppressive activity of the P53 gene rather than the “dominant” model, in which alteration of only one allele is sufficient for the development of malignancy.

scholarly journals p53 mutations are associated with histologic transformation of follicular lymphoma

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2289-2295 ◽  
Author(s):  
F Lo Coco ◽  
G Gaidano ◽  
DC Louie ◽  
K Offit ◽  
RS Chaganti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Low Grade ◽  
Diffuse Type ◽  
P53 Mutations ◽  
Clinical Progression ◽  
Hodgkin's Lymphomas

The majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.

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