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Mitochondrial DNA damage in non-melanoma skin cancer.

Durham SE, Krishnan KJ, Betts J, Birch-Machin MA - Br. J. Cancer (2003)

Bottom Line: 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.Currently, it is unclear whether mtDNA damage has a direct link to skin cancer or it may simply reflect an underlying nuclear DNA instability.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, School of Clinical and Laboratory Sciences, University of Newcastle, Leech Building, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.

ABSTRACT
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.

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Related in: MedlinePlus

MtDNA deletion spectrum of tumour and perilesional skin. A1 and A2: 11 kb PCR profile for BCC and SCC, respectively. B1 and B2: 5 kb PCR profile for BCC and SCC, respectively. Each panel of three lanes represents a single NMSC patient; lane 1=tumour, lane 2=dermis, lane 3=epidermis. The observed deletion profiles were reproducible over three independent PCR experiments. Molecular weight markers (Hyperladder I-range 10 kb–200 bp, Bioline Ltd, London UK) are the single lanes at the ends of each row of panels.
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fig1: MtDNA deletion spectrum of tumour and perilesional skin. A1 and A2: 11 kb PCR profile for BCC and SCC, respectively. B1 and B2: 5 kb PCR profile for BCC and SCC, respectively. Each panel of three lanes represents a single NMSC patient; lane 1=tumour, lane 2=dermis, lane 3=epidermis. The observed deletion profiles were reproducible over three independent PCR experiments. Molecular weight markers (Hyperladder I-range 10 kb–200 bp, Bioline Ltd, London UK) are the single lanes at the ends of each row of panels.

Mentions: The deletion spectrum was investigated in the mitochondrial genomes from the tumour samples and the histologically normal perilesional dermis and epidermis samples from each NMSC patient (total sample number is 30). Almost the entire mitochondrial genome was amplified in two fragments, namely 11 and 5.5 kb. The spectrum of deletions is visualised as a DNA ladder of PCR products on an agarose gel (Figure 1Figure 1


Mitochondrial DNA damage in non-melanoma skin cancer.

Durham SE, Krishnan KJ, Betts J, Birch-Machin MA - Br. J. Cancer (2003)

MtDNA deletion spectrum of tumour and perilesional skin. A1 and A2: 11 kb PCR profile for BCC and SCC, respectively. B1 and B2: 5 kb PCR profile for BCC and SCC, respectively. Each panel of three lanes represents a single NMSC patient; lane 1=tumour, lane 2=dermis, lane 3=epidermis. The observed deletion profiles were reproducible over three independent PCR experiments. Molecular weight markers (Hyperladder I-range 10 kb–200 bp, Bioline Ltd, London UK) are the single lanes at the ends of each row of panels.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376793&req=5

fig1: MtDNA deletion spectrum of tumour and perilesional skin. A1 and A2: 11 kb PCR profile for BCC and SCC, respectively. B1 and B2: 5 kb PCR profile for BCC and SCC, respectively. Each panel of three lanes represents a single NMSC patient; lane 1=tumour, lane 2=dermis, lane 3=epidermis. The observed deletion profiles were reproducible over three independent PCR experiments. Molecular weight markers (Hyperladder I-range 10 kb–200 bp, Bioline Ltd, London UK) are the single lanes at the ends of each row of panels.
Mentions: The deletion spectrum was investigated in the mitochondrial genomes from the tumour samples and the histologically normal perilesional dermis and epidermis samples from each NMSC patient (total sample number is 30). Almost the entire mitochondrial genome was amplified in two fragments, namely 11 and 5.5 kb. The spectrum of deletions is visualised as a DNA ladder of PCR products on an agarose gel (Figure 1Figure 1

Bottom Line: 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.Currently, it is unclear whether mtDNA damage has a direct link to skin cancer or it may simply reflect an underlying nuclear DNA instability.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, School of Clinical and Laboratory Sciences, University of Newcastle, Leech Building, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus