title: New mutations in the human p53 gene--a regulator of the cell cycle and carcinogenesis.
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 C(4) 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.
authors: Department of Molecular Immunology, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia. kachkine@yandex.ru
authors: K N
authors: KN
authors: Kashkin
authors: S V
authors: SV
authors: Khlgatian
authors: O V
authors: OV
authors: Gurova
authors: D V
authors: DV
authors: Kuprash
authors: S A
authors: SA
authors: Nedospasov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009367:Neoplasm Staging; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D017354:Point Mutation; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53