scholarly journals The 1995 Walter Hubert Lecture - molecular epidemiology of human cancer: insights from the mutational analysis of the p53 tumour-suppressor gene

1996 ◽  
Vol 73 (3) ◽  
pp. 261-269 ◽  
Author(s):  
CC Harris
Keyword(s):  
Molecular Epidemiology ◽  
Mutational Analysis ◽  
Human Cancer ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
P53 Tumour Suppressor Gene

Mutational analysis of the tumour suppressor gene MMAC1/PTEN in malignant myeloid disorders

2000 ◽  
Vol 65 (2) ◽  
pp. 109-113 ◽  
Author(s):  
Anni Aggerholm ◽  
Kirsten Grønbaek ◽  
Per Guldberg ◽  
Peter Hokland
Keyword(s):  
Mutational Analysis ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor

scholarly journals Characterising Mutational Spectra of Carcinogens in the Tumour Suppressor Gene TP53 Using Human TP53 Knock-in (Hupki) Mouse Embryo Fibroblasts

2019 ◽  
Vol 2 (4) ◽  
pp. 85 ◽  
Author(s):  
Hölzl-Armstrong ◽  
Kucab ◽  
Korenjak ◽  
Luijten ◽  
Phillips ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
Human Cancer ◽  
Atmospheric Oxygen ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
International Agency ◽  
Human Tumours ◽  
Clonal Cell Lines ◽  
Gene Tp53

DNA in dividing cells is prone to mutagenesis, with mutations making key contributions to human disease including cancer. The tumour suppressor gene TP53 is the most frequently mutated gene in human tumours. Here, we present a robust protocol for studying TP53 mutagenesis utilising human TP53 knock-in (Hupki) mouse embryonic fibroblasts (HUFs). In the HUF immortalisation assay (HIMA), primary HUFs are treated with known or suspected carcinogens at 3% oxygen and then transferred to 20% atmospheric oxygen to induce senescence. Cells containing mutations (e.g., in TP53) that allow bypassing of senescence eventually emerge as immortalised clonal cell lines after 2–3 months of serial passaging. As not all immortalised HUF cells contain TP53 mutations, we developed a Nutlin-3a counter-screen to select for TP53-mutated clones prior to sequencing. TP53 mutation spectra generated can be compared with those of human tumours recorded in the International Agency for Research on Cancer TP53 mutation database. Environmental mutagens that have demonstrated and validated the utility of the HIMA include ultraviolet radiation, aristolochic acid, and benzo[a]pyrene. The TP53 mutation patterns induced by these mutagens in the HIMA corresponded to those found in human tumours from patients exposed to these mutagens. The approach presented helps to deepen our understanding of human cancer aetiology.

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