cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer
| العنوان: | cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer |
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| المؤلفون: | Piotr Rieske, Izabela Zawlik, Grażyna Pasz-Walczak, Robert Stawski, Malgorzata Szybka, Dominika Kulczycka-Wojdala, Dorota Jesionek-Kupnicka, Magdalena Zakrzewska, Radzisław Kordek, Pawel P. Liberski |
| المصدر: | BMC Cancer, Vol 9, Iss 1, p 278 (2009) BMC Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Cancer Research, DNA, Complementary, Sequence analysis, Mutation, Missense, Loss of Heterozygosity, Biology, Gene mutation, medicine.disease_cause, lcsh:RC254-282, DNA sequencing, Loss of heterozygosity, Complementary DNA, Genetics, medicine, Humans, Missense mutation, Gene, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Genes, p53, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Molecular biology, Gene Expression Regulation, Oncology, Codon, Nonsense, Tumor Suppressor Protein p53, Colorectal Neoplasms, Research Article |
| الوصف: | Background Recently published data showed discrepancies beteween P53 cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers. Methods To this end, we analyzed 23 colorectal cancers for P53 mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry. Results We found P53 gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of P53 mRNA was present in samples with and without P53 mutations. Conclusion In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated P53 mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without P53 mutation (normal cells and cells showing K-RAS and/or APC but not P53 mutation) in samples presenting P53 mutation; 3, heterozygous or hemizygous mutations of P53 gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in P53 cDNA and DNA sequencing analysis. |
| تدمد: | 1471-2407 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6574b08f98d05de5887cc31c7c47d5b8Test https://doi.org/10.1186/1471-2407-9-278Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6574b08f98d05de5887cc31c7c47d5b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712407 |
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