Radiation-induced Basal Cell Carcinoma Research Articles

Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma.

Research in normal tissue radiobiology is in continuous progress to assess cellular response following ionizing radiation exposure especially linked to carcinogenesis risk. This was observed among patients with a history of radiotherapy of the scalp for ringworm who developed basal cell carcinoma (BCC). However, the involved mechanisms remain largely undefined. We performed a gene expression analysis of tumor biopsies and blood of radiation-induced BCC and sporadic patients using reverse transcription-quantitative PCR. Differences across groups were assessed by statistical analysis. Bioinformatic analyses were conducted using miRNet. We showed a significant overexpression of the FOXO3a, ATM, P65, TNF-α and PINK1 genes among radiation-induced BCCs compared to BCCs in sporadic patients. ATM expression level was correlated with FOXO3a. Based on receiver-operating characteristic curves, the differentially expressed genes could significantly discriminate between the two groups. Nevertheless, TNF-α and PINK1 blood expression showed no statistical differences between BCC groups. Bioinformatic analysis revealed that the candidate genes may represent putative targets for microRNAs in the skin. Our findings may yield clues as to the molecular mechanism involved in radiation-induced BCC, suggesting that deregulation of ATM-NF-kB signaling and PINK1 gene expression may contribute to BCC radiation carcinogenesis and that the analyzed genes could represent candidate radiation biomarkers associated with radiation-induced BCC.

Narrative review: mechanism of ultraviolet radiation-induced basal cell carcinoma

Background and Objective: Basal cell carcinoma (BCC) is the most widespread malignant skin cancer and also the most common cancer in adults. Although its mortality rate is low, its incidence is increasing, especially in Caucasians. Among many risk factors, ultraviolet radiation (UVR) is the essential factor in forming BCC. However, the molecular mechanisms leading to transformation are not fully understood. This review provides a comprehensive description of the interaction of UVR and genetic features in the pathogenesis of BCC, and specifically, current advances in molecular therapy based on these mechanisms are introduced.

Comparison of COX2 expression in radiation induced basal cell carcinoma and non-radiation induced basal cell carcinoma

Background: Radiation-induced basal cell carcinoma (BCC) can be multiple, large, and recurring, which complicates its treatment in some cases. According to reports on the role of cyclooxygenase 2 (COX2) inhibitors in the treatment or prevention of non-melanoma skin cancers and considering the fact that COX2 expression has not been evaluated in radiation-induced basal cell carcinoma, weset out to assess the expression of COX2 in these lesions. Methods: In this study, COX2 expression was assessed by immunohistochemistry using anti-COX2 antibody on paraffinembedded blocks of 86 patients referred to Emam Reza Hospitalin Mashhad with BCC diagnosis by pathological examination (43 patients with and 43 without a history of radiotherapy) followed by semi-quantitative evaluation of COX2. Results: In our study, COX2 expression score was significantly higher in patients with a history of radiotherapy than those without radiotherapy (P<0.001). No correlation was found between theintensity and percentage of staining with sex, age, site of lesion, recurrence, and pathology of the tumor. Conclusion: Given the higher expression level of COX2 in the radiation-induced BCC patients, the use of COX2 inhibitors in these individuals may be effective in the incidence, recurrence, or treatment of BCC.

Radiation-induced basal cell carcinoma.

Background:The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. A variety of cancers including basal cell carcinoma (BCC) are seen years after this treatment.Objective:We sought to determine the clinical characteristics of BCCs among irradiated patients.Methods:The clinical records of all patients with BCC in a clinic in north of Iran were reviewed.Results:Of the 58 cases of BCC, 29 had positive history for radiotherapy in their childhood. Multiple BCCs were seen in 79.3% and 10.3% of patients with history and without history of radiotherapy, respectively.Conclusions:X-ray radiation is still a major etiologic factor in developing BCC in northern Iran. Patients with positive history for radiotherapy have higher rate of recurrence.

Genetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice

Ptch1 germ-line mutations in mice predispose to radiation-induced basal cell carcinoma of the skin, with tumor incidence modulated by the genetic background. Here, we examined the possible mechanisms underlying skin response to radiation in F1 progeny of Ptch1(neo67/+) mice crossed with either skin tumor-susceptible (Car-S) or -resistant (Car-R) mice and X-irradiated (3 Gy) at 2 days of age or left untreated. We conducted a gene expression profile analysis in mRNA samples extracted from the skin of irradiated or control mice, using Affymetrix whole mouse genome expression array. Confirmation of the results was done using real-time reverse-transcriptase polymerase chain reaction. Analysis of the gene expression profile of normal skin of F1 mice at 4 weeks of age revealed a similar basal profile in the nonirradiated mice, but alterations in levels of 71 transcripts in irradiated Ptch1(neo67/+) mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1(neo67/+) mice of the Car-S cross. These results indicate that neonatal irradiation causes a persistent change in the gene expression profile of the skin. The tendency of mice genetically resistant to skin tumorigenesis to show a more complex pattern of transcriptional response to radiation than do genetically susceptible mice suggests a role for this response in genetic resistance to basal cell tumorigenesis.

Successful use of radiotherapy for radiation-induced basal cell carcinoma of the scalp

Conflict of interest: none declared. In an interesting contribution published in Clinical and Experimental Dermatology,1 a case of basal cell carcinoma (BCC) of the scalp arising after radiotherapy for tinea capitis and successfully treated with radiotherapy was described. In the same article, the question about the management of patients with radiation‐induced skin malignancies was discussed, with considerations we fully share. The authors, however, stated that they were not able to find ‘published reports of successful treatment of radiation‐induced skin cancers with radiotherapy’. Therefore, we think it useful to report that we treated with radiotherapy two women with BCCs of the scalp, which appeared, respectively, 52 and 76 years after end of radiation therapy received for tinea capitis.2 The lesions were treated with contact X‐ray therapy (dose per fraction 5 Gy twice/week, giving a total dose 55 Gy). For the two women, the size of the irradiation fields was 10 and 35 mm, respectively, focus skin distance 15 and 50 mm, half‐value depth 2 and 12 mm, voltage 55 and 60 kV, and current was 4 mA for both. Both lesions are in complete remission 24 and 54 months, respectively, after the end of radiotherapy. To date, the cosmetic result has been judged as good in both lesions.

PTCH (patched) and XPA genes in radiation-induced basal cell carcinomas

A study of X-irradiated tinea capitis patients has identified a small subgroup (about 1.5%) of people at high risk for developing multiple basal cell carcinomas (BCCs). Among 1680 Caucasians who received about 3 Gy of low voltage X-ray, the incidence of BCCs, 35 years after exposure, was 0.10 tumors per person. A random distribution indicates that no one should have developed three or more BCCs and yet 25 with three or more were observed. Among three selected from the latter group, one presented with five previously unreported BCCs; one presented with four; and one presented with one. Varied patterns of loss of heterozygosity (LOH) were found in the BCCs from all three patients in the region of the PTCH and xeroderma pigmentosum A ( XPA) genes in chromosome region 9q22.3–31. The subject with five BCCs reported that 25 BCCs had previously been removed. Amplification primers for XPA were picked from intronic sequences and positive SSCP results were followed-up by sequencing the identified regions to establish the exact nature of the mutation. A large number of negative SSCP results were sequenced, but no mutations undetected by SSCP were found. Normal blood DNA of the subject with five BCCs showed a 14 base deletion in exon 6 of the XPA gene, strongly suggesting XPA heterozygosity. Biopsy samples of the BCCs showed the same 14 base deletion in all five BCCs. Allelic identification verified that the normal XPA allele was missing in two of two BCCs selected for testing. These data imply that a mutational inactivation of one XPA allele increased the susceptibility to BCC induction by ionizing radiation, possibly because the normal XPA allele was lost in the same deletional event that produced LOH in the PTCH region. These findings support the idea that the lost event associated with LOH at 9q22.3 frequently (5/5) includes both the PTCH and XPA loci. Frequently, an XPA allele located within about 3 megabases distal to PTCH is lost along with the PTCH gene. Overall, these results suggest how inactivation of the XPA gene may play an important role in susceptibility to BCC induction by increasing the UV-induced mutational rate of PTCH or other cancer-relevant genes (work supported by NIEHS, NCI, and EPA).

Carcinogen-specific mutation pattern in the p53 tumour suppressor gene in UV radiation-induced basal cell carcinoma.

Basal cell carcinoma (BCC) is mainly caused by high and long-term UV radiation. UV radiation causes DNA damage in various genes. Mutations of the p53 tumour suppressor gene have been identified in a wide variety of human cancers. The aim of the study was to analyse specific p53 mutations in BCCs in workers exposed to high and long-term UV radiation. The mutation pattern of the p53 tumour suppressor gene was analysed in tissue from 12 patients with UV-related BCC. All patients had a suspected occupational disease notified within the period 1995-1999. As a control, 20 BCC skin samples removed from areas definitively unexposed to sunlight were analysed. The specific mutations were determined by direct sequencing of codon 4 to 9 of the p53 gene in carcinomatous and adjacent non-neoplastic tissue after microdissection. Immunohistochemical analysis was performed to detect p53 protein. p53 mutations were detected in 7/12 cases (58%). Point mutations were found in six cases (50%). In one case a deletion of 24 base pairs was observed. The most frequent mutations we found were CC-->TT base-pair changes in four and C-->T mutations in two cases. Within the control group specific p53 mutations were found in 11 cases (55%) without any C-->T predominance. No case showed CC-->TT mutations. Mutations of the p53 tumour suppressor gene in UV-associated BCC are frequent events. A predominance of C-->T mutations and tandem CC-->TT base-pair changes were observed in the sunlight-exposed cases only supporting the idea of site-directed mutagenesis by UV radiation in human BCC.