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New mutations in the human p53 gene — a regulator of the cell cycle and carcinogenesis

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Abstract

Mutations in the tumor suppressor gene p53 often lead to disarrangement of the cell cycle and of genetic integrity control of cells that may contribute to tumor development. We studied p53 gene mutations in 26 primary tumors of colorectal cancer patients. Mutations in p53 were found in 17 tumors (65.4%). All point mutations affected the DNA binding domain of p53 and were localized in exons 4–8 of the gene. Mutant p53 isoforms with altered domain structure and/or with alternative C-terminus arising from frameshift mutations or abnormal splicing were found in six tumors. Mutations Leu111Gln and Ser127Phe were shown in colorectal cancer for the first time. Isoforms p53–305 with C4 insertion in codons 300/301 and p53i9* including an additional 44 nucleotides of the 3′-end of intron 9 were discovered for the first time. Mutations of p53 were associated with lymph node metastases and III/IV stage of tumors that are signs of unfavorable prognosis in colorectal cancer.

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Abbreviations

CRC:

human colorectal cancer

ECR:

evolutionary conserved region

n.:

nucleotide

Ti:

transition

Tv:

transversion

TNM:

classification of malignant tumors by International Union Against Cancer, 2002

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Author information

Authors and Affiliations

  1. Department of Molecular Immunology, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Moscow, Russia

    K. N. Kashkin, S. V. Khlgatian & S. A. Nedospasov

  2. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 119997, Moscow, Russia

    K. N. Kashkin

  3. 24th Municipal Hospital, Strastnoi Bul’var 15/29, 103006, Moscow, Russia

    O. V. Gurova

  4. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991, Moscow, Russia

    D. V. Kuprash & S. A. Nedospasov

Authors
  1. K. N. Kashkin
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  2. S. V. Khlgatian
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  3. O. V. Gurova
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  4. D. V. Kuprash
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  5. S. A. Nedospasov
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Correspondence to K. N. Kashkin.

Additional information

Published in Russian in Biokhimiya, 2007, Vol. 72, No. 3, pp. 346–357.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM06-272, January 14, 2007.

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Kashkin, K.N., Khlgatian, S.V., Gurova, O.V. et al. New mutations in the human p53 gene — a regulator of the cell cycle and carcinogenesis. Biochemistry Moscow 72, 282–292 (2007). https://doi.org/10.1134/S0006297907030054

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  • DOI: https://doi.org/10.1134/S0006297907030054

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