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  • Title: Mutational analysis of the human cyclin-dependent kinase inhibitor p27kip1 in primary breast carcinomas.
    Author: Ferrando AA, Balbín M, Pendás AM, Vizoso F, Velasco G, López-Otín C.
    Journal: Hum Genet; 1996 Jan; 97(1):91-4. PubMed ID: 8557269.
    Abstract:
    The human p27kip1 gene encodes a cyclin-dependent kinase inhibitor implicated in the negative regulation of the cell cycle. In order to elucidate the possible role of p27 mutations in the development or progression of human breast cancer, we have studied the occurrence of genetic abnormalities in this gene in a series of 30 primary breast carcinomas. Direct sequence analysis of the polymerase chain reaction amplified human p27 gene revealed the occurrence of two sequence variations with respect to the reported sequence; both variants were also present in the lymphocyte DNA from the same patients. First, a silent G to A change at codon 142 (Thr) was detected in a single case. Second, a T to G transversion at codon 109, resulting in a Val to Gly change, was observed in eight tumour DNA samples (26%) and in 31 out of 80 unrelated normal individuals (39%). This latter change creates a Bg/I restriction site that might be useful for genetic analysis of human tumours. Despite the occurrence of these polymorphisms, we did not however find any evidence of somatic mutations in the coding region of the p27 gene. On the basis of these results, we suggest that alterations in the integrity of the human p27 gene are not common events in human breast carcinomas.
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