Yasuhiro Matsumura

Increase in radiation sensitivity of human malignant melanoma cells by expression of wild-type p16 gene

The influence of wild-type p16 expression on the radiation sensitivity of human melanoma cell lines was investigated. MeWo cells, which alone expressed intrinsic wild-type p16 among six melanoma cell lines examined, showed higher radiosensitivity in comparison with the other five melanoma cells. The introduction of human wild-type p16 cDNA into A875 cells, which homozygously lost p16 genes, and AKI cells, which retained p16 gene but did not express p16 mRNA, led to increased sensitivity of those cells to X-ray irradiation. The radiosensitizing effect by the p16 introduction to those cells was prominent after rather higher doses of X-rays (8 and 10 Gy). In both A875 and AKI, no significant difference in sensitivities to UVC and cisplatin was observed between the parental and p16-transfectant cells. These results suggest that the loss or dysfunction of p16 gives melanoma cells the radioresistant characteristics.

Characterization of p53 gene mutations in basal-cell carcinomas : Comparison between sun-exposed and less-exposed skin areas

Mutations in the p53 gene in 32 basal‐cell carcinomas (BCC) developed in Japanese patients were identified by the polymerase chain reaction and single‐strand‐conformation polymorphism analysis, followed by sequencing the DNA. Among 16 BCC developed in continuously sun‐exposed areas, 6 tumors showed 7 base substitutions, most of which were G:C to A:T transitions, mainly at the dipyrimidine sites. Seven out of 16 BCC developed in less‐exposed areas showed 8 base substitutions, but the majority (75.0%) of them were transversions. These results suggest that the mutation in the p53 gene plays a significant role in the tumorigenesis of BCC developed in less‐exposed areas as well as those in sun‐exposed areas in Japanese patients. There must be therefore causative factors other than UV irradiation for BCC in less‐exposed areas.

PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease

To identify cancer‐related genes that are involved in the carcinogenesis of extramammary Pagets disease (EMPD), we compared mRNA expression profiles of EMPD lesions and corresponding normal skin using cDNA array. Sixty‐eight genes were highly expressed (>5‐fold) in EMPD lesions compared to normal skin, and 40 genes were expressed less than one‐fifth in EMPD lesions. Among them, PIG7/LITAF mRNA was overexpressed in 3 of 4 EMPD cases. PIG7/LITAF transcription is induced by p53 expression and has been implicated in the p53‐induced apoptotic pathway. Since expression of p53 mRNA and p53 protein was not high in any of the 3 EMPD samples compared to the intact skin of the same patient, we analyzed PIG7/LITAF cDNA mutations among 12 EMPD samples (including the former 4) by PCR‐SSCP. Three samples showed shifted bands (2 had point mutations leading to amino acid substitutions and 1 had a silent mutation). One sample with amino acid substitution overexpressed PIG7/LITAF mRNA in cDNA array analysis and RT‐PCR. PIG7/LITAF mRNA expression is confined to tumor cells in in situ mRNA hybridization analysis. These results indicate that genetic disorder and overexpression of PIG7/LITAF may be involved in EMPD carcinogenesis.

Epidermolysis Bullosa Acquisita (EBA) with Nonclassical Distribution of Eruptions

The skin lesions in epidermolysis bullosa acquisita (EBA), a mechanobullous disease, often show acral distribution. Recently, we experienced a case of EBA in which most of the skin lesions were located on the trunk. We reviewed the distribution of the skin eruptions in 58 reported cases of EBA. Although the extensor surfaces of the extremities are the most common site, there were some cases with non‐acral distribution. These “nonclassical” cases should also be considered in the clinical diagnosis of EBA and other bullous diseases.