Compilation of somatic mutations of the CDKN2 gene in human cancers: Non-random distribution of base substitutions

✍ Scribed by Pamela M. Pollock; John V. Pearson; Nicholas K. Hayward

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 1011 KB
• Volume: 15
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199602)15:2<77::aid-gcc1>3.0.co;2-0

✦ Synopsis

The CDKff2 gene, encoding the cyclin-dependent kinase inhibitor p16. is a tumour suppressor gene that maps to chromosome band 9p2 I -p22. The most common mechanism o f inactivation of this gene in human cancers is through homorygous deletion; however, in a smaller proportion of tumours and tumour cell lines intragenic mutations occur. In this study we have compiled a database of over 120 published point mutations in the CDKN2 gene from a wide variety of tumour types. A further 50 deletions, insertions, and splice mutations in CDKNZ have also been compiled. Furthermore, we have standardised the numbering of all mutations according to the full-length I56 amino acid form of p 16. From this study we are able to define several hot spots, some of which occur at conserved residues within the ankyrin domains of p 16. While many of the hotspots are shared by a number of cancers, the relative importance of each position varies, possibly reflecting the role of different carcinogens in the development of certain tumours. As reported previously, the mutational spectrum of CDKN2 in melanomas differs from that of internal malignancies and supports the involvement of UV in melanoma tumorigenesis. Notably, 52% of all substitutions in melanoma-derived samples occurred at just six nucleotide positions. Nonsense mutations comprise a comparatively high proportion of mutations present in the CDKff2 gene, and possible explanations for this are discussed.