scholarly journals Biological and clinical importance of the p53 tumor suppressor gene

1996 ◽  
Vol 42 (6) ◽  
pp. 858-868 ◽  
Author(s):  
V E Velculescu ◽  
W S El-Deiry
Keyword(s):  
Dna Damage ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Chemotherapeutic Agents ◽  
Cellular Growth ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene ◽  
P53 Antibodies

Abstract The p53 tumor suppressor gene controls cellular growth after DNA damage through mechanisms involving growth arrest and apoptosis. Mutations that inactivate p53 occur commonly in virtually all human malignancies and can be detected by sequencing of the p53 gene, immunohistochemical staining of tumor tissue with anti-p53 antibodies, single-strand conformation polymorphisms, or other biological assays. Identification of p53 mutation in the germ line is diagnostic of the cancer-prone Li-Fraumeni syndrome. Alterations of the p53 gene result in defective cellular responses after DNA damage and predispose cells to dysregulated growth, tumor formation and progression, and potential resistance (of tumor cells) to certain chemotherapeutic agents or ionizing radiation. A variety of tumors involving mutant p53 have a worse prognosis than tumors of the same type containing no p53 mutations. New diagnostic and therapeutic strategies are evolving as the p53 pathways of cell-cycle arrest and apoptosis become elucidated.

scholarly journals Chemical selectivity of nucleobase adduction relative to in vivo mutation sites on exon 7 fragment of p53 tumor suppressor gene

2015 ◽  
Vol 6 (10) ◽  
pp. 5554-5563 ◽  
Author(s):  
Spundana Malla ◽  
Karteek Kadimisetty ◽  
You-Jun Fu ◽  
Dharamainder Choudhary ◽  
Ingela Jansson ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
P53 Gene ◽  
Suppressor Gene ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene ◽  
Chemical Selectivity

A 32-bp fragment of P53 gene reacted with benzo[a]pyrene metabolite BPDE was analyzed by LC-MS/MS. Chemically reactive sites were similar to frequently mutated codons in tumors.

Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.

1994 ◽  
Vol 12 (5) ◽  
pp. 925-930 ◽  
Author(s):  
J F McIntyre ◽  
B Smith-Sorensen ◽  
S H Friend ◽  
J Kassell ◽  
A L Borresen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
P53 Gene ◽  
Predictive Testing ◽  
Germline Mutations ◽  
Suppressor Gene ◽  
P53 Mutations ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene ◽  
First Degree Relatives

PURPOSE We investigated the possibility that a significant proportion of children with osteosarcoma harbor germline mutations of the p53 tumor suppressor gene and, therefore, this subgroup of pediatric cancer patients should be considered for large-scale predictive testing. PATIENTS AND METHODS Genomic DNA extracted from peripheral-blood leukocytes from 235 unselected children with osteosarcoma from 33 institutions were screened for the presence of germline p53 mutations using constant denaturant gel electrophoresis (CDGE). Exons 5 through 8 were evaluated in all patients and exon 2 and exon 9 were analyzed in 59 and 95 patients, respectively. Those samples that showed aberrant migration on CDGE were sequenced or analyzed by restriction enzyme digestion of polymerase chain reaction (PCR) products to confirm the nature of the gene alteration. RESULTS In 18 samples, CDGE showed fragments of the p53 gene with altered electrophoretic mobilities compared with wild-type p53. DNA sequencing showed that 11 samples had an identical, previously described polymorphism. The other seven contained heterozygous p53 mutations located in exon 5 (n = 3), exon 6 (n = 1), exon 7 (n = 1), and exon 8 (n = 2). Six alterations were missense mutations and one was a nonsense mutation. Three of these patients had first-degree relatives with cancer. One of these three kindreds had a family history consistent with Li-Fraumeni syndrome (LFS). CONCLUSION We identified germline p53 mutations in seven of 235 (3.0%) children with osteosarcoma. Four of these mutations were found in patients who did not have first-degree relatives with cancer. Although genetic transmission of the altered p53 gene could not be tested in this survey because of how it was designed, it is possible that predictive testing for p53 mutations could identify unaffected relatives of gene carriers who also have a high risk for the development of cancer. This study provides evidence for the importance of considering children with osteosarcoma for predictive testing for germline p53 mutations.

scholarly journals p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 4012-4020 ◽  
Author(s):  
M Chilosi ◽  
C Doglioni ◽  
A Magalini ◽  
G Inghirami ◽  
M Krampera ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gene Function ◽  
Gene Mutations ◽  
P53 Gene ◽  
Suppressor Gene ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene ◽  
Hodgkin's Lymphomas ◽  
Tumor Suppressor Gene Function

p21WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs;253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single- strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30-NHL and in only 8 of 36 (22.2%) CD30+cases, which were mostly anaplastic large-cell lymphomas. A consistent number (> 10%) of p21WAF1-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+cases (25/36 [69.4%]), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30-group, neoplastic cells were p53+/p21-. In all of these cases, the p53+cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.

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