Mitochondrial DNA damage in non-melanoma skin cancer
| Autor: | Joanne Betts, Kim J. Krishnan, Mark A. Birch-Machin, Steve E. Durham |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Mitochondrial DNA Pathology medicine.medical_specialty Skin Neoplasms DNA damage MtDNA Human skin Biology DNA Mitochondrial tandem duplications Gene duplication medicine Humans Aged Aged 80 and over skin cancer integumentary system Point mutation Molecular and Cellular Pathology Middle Aged medicine.disease Molecular biology Heteroplasmy perilesional skin Nuclear DNA Oncology Tandem Repeat Sequences deletion spectrum Skin cancer Gene Deletion DNA Damage |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600773 |
| Popis: | Mitochondrial DNA (mtDNA) damage, predominantly encompassing point mutations, has been reported in a variety of cancers. Here we present in human skin, the first detailed study of the distribution of multiple forms of mtDNA damage in nonmelanoma skin cancer (NMSC) compared to histologically normal perilesional dermis and epidermis. We present the first entire spectrum of deletions found between different types of skin tumours and perilesional skin. In addition, we provide the first quantitative data for the incidence of the common deletion as well as the first report of specific tandem duplications in tumours from any tissue. Importantly, this work shows that there are clear differences in the distribution of deletions between the tumour and the histologically normal perilesional skin. Furthermore, DNA sequencing of four mutation 'hotspot' regions of the mitochondrial genome identified a previously unreported somatic heteroplasmic mutation in an SCC patient. In addition, 81 unreported and reported homoplasmic single base changes were identified in the other NMSC patients. Unlike the distribution of deletions and the heteroplasmic mutation, these homoplasmic mutations were present in both tumour and perilesional skin, which suggests that for some genetic studies the traditional use of histologically normal perilesional skin from NMSC patients may be limited. Currently, it is unclear whether mtDNA damage has a direct link to skin cancer or it may simply reflect an underlying nuclear DNA instability. |
| Databáze: | OpenAIRE |
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