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Miochondrial DNA mutations in oral squamous cell carcinoma / Sarah, Prior; Paul, Lewis

Carcinogenesis, Volume: 27, Issue: 5, Pages: 945 - 950

Swansea University Authors: Sarah, Prior, Paul, Lewis

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DOI (Published version): 10.1093/carcin/bgi326

Abstract

It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations within the ND2 gene of histologically normal parotid salivary gland tissue of smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral squamous cell carcinoma (SCC) is strongly related to cigarette smoking...

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Published in: Carcinogenesis
Published: Oxford journals 2006
Online Access: http://carcin.oxfordjournals.org/content/27/5/945.abstract
URI: https://cronfa.swan.ac.uk/Record/cronfa10724
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spelling 2014-12-05T14:40:31.5036580 v2 10724 2012-05-09 Miochondrial DNA mutations in oral squamous cell carcinoma cdda101035997acfaa6fdf17097f52b2 0000-0001-8703-8092 Sarah Prior Sarah Prior true false 46dfc22d7468f247c390ba0c6cd8fba6 0000-0002-6360-3832 Paul Lewis Paul Lewis true false 2012-05-09 PMSC It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations within the ND2 gene of histologically normal parotid salivary gland tissue of smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral squamous cell carcinoma (SCC) is strongly related to cigarette smoking; therefore, we used PCR and direct sequencing to establish whether mtDNA mutations were also present in oral SCC which could be used as additional biomarkers for smoking-associated DNA damage. In addition to searching for mutations in the ND2 gene, the mitochondrial D-Loop was also analysed. Three mutation hotspots were observed in the D-Loop at nt 146, 152 and 186, two of which (nt 146 and 152) have also been implicated in oesophageal SCC, another smoking-related cancer. The mutation hotspot observed at nt 186 has not previously been reported in other tumours. Furthermore, we show that the mutations previously reported within the ND2 gene in normal parotid tissue of smokers were not evident in these samples, but that a mutation hotspot occurs at nucleotide 4917 in oral SCC. We also show that D-Loop mutations occur predominantly in male smokers and female non-smokers and that this association with gender is statistically significant (P = 0.003). We conclude that the mtDNA mutation hotspots found in this study, in particular nt 186, are potential biomarkers for oral SCC. However, owing to gender-specific differences in occurrence in smokers and non-smokers, and a lack of environmental smoking history, in general, it is difficult to associate these mutations with mtDNA damage induced by smoking. If the mutations observed in the subset of male patients are smoking induced, given our previous findings, mutation hotspots in the ND2 gene may be tissue specific suggesting the causative mutagens for mtDNA damage within these tissues are likely to be different. Journal Article Carcinogenesis 27 5 945 950 Oxford journals mitochondrial DNA; squamous cell carcinoma 31 12 2006 2006-12-31 10.1093/carcin/bgi326 http://carcin.oxfordjournals.org/content/27/5/945.abstract COLLEGE NANME Medicine COLLEGE CODE PMSC Swansea University 2014-12-05T14:40:31.5036580 2012-05-09T09:25:01.7172825 Swansea University Medical School Medicine Sarah Prior 0000-0001-8703-8092 1 Paul Griffiths 2 Julia Baxter 3 Pru Baxter 4 Simon Hodder 5 Keith Silvester 6 Paul Lewis 0000-0002-6360-3832 7
title Miochondrial DNA mutations in oral squamous cell carcinoma
spellingShingle Miochondrial DNA mutations in oral squamous cell carcinoma
Sarah, Prior
Paul, Lewis
title_short Miochondrial DNA mutations in oral squamous cell carcinoma
title_full Miochondrial DNA mutations in oral squamous cell carcinoma
title_fullStr Miochondrial DNA mutations in oral squamous cell carcinoma
title_full_unstemmed Miochondrial DNA mutations in oral squamous cell carcinoma
title_sort Miochondrial DNA mutations in oral squamous cell carcinoma
author_id_str_mv cdda101035997acfaa6fdf17097f52b2
46dfc22d7468f247c390ba0c6cd8fba6
author_id_fullname_str_mv cdda101035997acfaa6fdf17097f52b2_***_Sarah, Prior
46dfc22d7468f247c390ba0c6cd8fba6_***_Paul, Lewis
author Sarah, Prior
Paul, Lewis
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container_title Carcinogenesis
container_volume 27
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container_start_page 945
publishDate 2006
institution Swansea University
doi_str_mv 10.1093/carcin/bgi326
publisher Oxford journals
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
url http://carcin.oxfordjournals.org/content/27/5/945.abstract
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description It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations within the ND2 gene of histologically normal parotid salivary gland tissue of smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral squamous cell carcinoma (SCC) is strongly related to cigarette smoking; therefore, we used PCR and direct sequencing to establish whether mtDNA mutations were also present in oral SCC which could be used as additional biomarkers for smoking-associated DNA damage. In addition to searching for mutations in the ND2 gene, the mitochondrial D-Loop was also analysed. Three mutation hotspots were observed in the D-Loop at nt 146, 152 and 186, two of which (nt 146 and 152) have also been implicated in oesophageal SCC, another smoking-related cancer. The mutation hotspot observed at nt 186 has not previously been reported in other tumours. Furthermore, we show that the mutations previously reported within the ND2 gene in normal parotid tissue of smokers were not evident in these samples, but that a mutation hotspot occurs at nucleotide 4917 in oral SCC. We also show that D-Loop mutations occur predominantly in male smokers and female non-smokers and that this association with gender is statistically significant (P = 0.003). We conclude that the mtDNA mutation hotspots found in this study, in particular nt 186, are potential biomarkers for oral SCC. However, owing to gender-specific differences in occurrence in smokers and non-smokers, and a lack of environmental smoking history, in general, it is difficult to associate these mutations with mtDNA damage induced by smoking. If the mutations observed in the subset of male patients are smoking induced, given our previous findings, mutation hotspots in the ND2 gene may be tissue specific suggesting the causative mutagens for mtDNA damage within these tissues are likely to be different.
published_date 2006-12-31T03:24:23Z
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