p53 mutation spectrum in Japanese Bowen's disease suggests a role for mutagens other than ultraviolet light

Abstract

The Japanese have a much lower incidence of nonmelanoma skin cancers (NMSCs) than Caucasians, presumably due in part to their skin type conferring relative protection from ultraviolet light radiation (UVR). To examine the contribution of environmental or endogenous mutagens other than UVR, which are expected to be relatively more important to the overall burden of NMSCs in the Japanese, we directly sequenced exons 5-8 of the p53 tumour suppressor gene in 29 Japanese patients with Bowen's disease, an in situ squamous-cell carcinoma of the skin. We found 9 mutations, including two CC:GG to TT:AA tandem transitions (presumably related to UVR), 3 transversions and 4 frameshift mutations. The mutational spectrum seen in our study contrasts with that we previously found in Bowen's disease from a Caucasian population, in keeping with a different aetiology for Bowen's disease in the respective populations. The unexpectedly high prevalence of frameshift mutations suggests that environmental mutagens other than UVR that preferentially induce deletion or insertion mutations may play an important role in the tumorigenesis of Japanese Bowen's disease, and warrants further investigation.

Human papillomavirus infection in Bowen disease: Negative p53 expression, not p16INK4a overexpression, is correlated with human papillomavirus‐associated Bowen disease

“…42 TP53 gene mutations were reported to be common in BD as well and are considered to be an early event in the development of the condition. 43,44 In our study, positive nuclear p53 staining was observed in 62.4% of BD lesions. In line with our results, previous studies of BD detected high frequencies of p53 expression, ranging 44-90%.…”

A Patient with TP53 Germline Mutation Developed Bowen's Disease and Myelodysplastic Syndrome with Myelofibrosis after Chemotherapy against Ovarian Cancer

“…Bowen's disease is one of the precursors of nonmelanoma skin cancer (19), and it has been reported that 31 to 47% of Bowen's disease cases show TP53 mutations (9)(10)(11). The results of immunostaining in our case suggested that p53 promotes the development of Bowen's disease as p53 had accumulated in the nuclei of the lesion but not in normal skin.…”

The temporal and spatial distribution of p21WAF expression in skin appendages

“…Ten cases of histologically confirmed Bowen’s disease that were paraffin embedded were microdissected and DNA extracted as described. 28 Samples were screened for loss of heterozygosity using the polymorphic marker D17S796 (17p), with normal skin samples providing a germline comparison. 9 , 28 Samples showing loss of heterozygosity were selected for further analysis and exons 5–9 of p53 manually sequenced as previously described.…”