Analysis of Sdhd and Mmp12 in an Affected Solar Keratosis and Control Cohort

  • N.A. Lintell
  • D.J. Maguire
  • L.R. Griffiths
  • M. McCabe
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 599)


The incidence of Squamous Cell Carcinoma (SCG) is growing in certain populations to the extent that it is now the most common skin lesion in young men and women in high ultraviolet exposure regions such as Queensland. In terms of incidence up to 40% of the Australian population over 40 years of age is thought to possess the precancerous Solar Keratosis (SK) lesion and with a small, but significant, chance of progression into SCC, understanding the genetic events that play a role in this process is essential. The major aims of this study were to analyse whole blood derived samples for DNA aberrations in genes associated with tumour development and cellular maintenance, with the ultimate aim of identifying genes associated with non-melanoma skin cancer development. More specifically the first aim of this project was to analyse the SDHD and MMP12 genes via Dual-Labelled Probe Real-Time PCR for copy number aberrations in an affected Solar Keratosis and control cohort. It was found that 12 samples had identifiable copy-number aberrations in either the SDHD or MMP12 gene (this means that a genetic section of either of these two genes is aberrantly amplified or deleted), with five of the samples exhibiting aberrations in both genes. The significance of this study is the contribution to the knowledge of the genetic pathways that are malformed in the progression and development of the pre-cancerous skin lesion Solar Keratosis.


Comparative Genomic Hybridisation Genetic Gain MMP12 Gene Genetic Loss Solar Keratosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Frost C, Williams G and Green A. High incidence and regression rates of solar keratoses in a Queensland community. J. Invest. Dermatol. 115 (2000), pp. 273-277.PubMedCrossRefGoogle Scholar
  2. 2.
    Rosen RH and Studniberg H. Solar keratoses: analysis in a dermatological practice in Australia Nutrition. 44 (2003), pp: 34-39.Google Scholar
  3. 3.
    Gosslau A and Chen KY. Nutraceuticals, apoptosis, and disease prevention. Oral Oncology. 20 (2004), pp. 95-102.Google Scholar
  4. 4.
    Modica-Napolitano JS and Singh KK. Mitochondrial dysfunction in cancer. Mitochondrion. (2004), pp. 1-8.Google Scholar
  5. 5.
    Warburg O. The origin of cancer cells. Science. 123 (1956), pp. 309-314.PubMedCrossRefGoogle Scholar
  6. 6.
    Warburg O, Posenor K and Nehelein E. üden Stoffwechsel der Carcinomzelle. Biochem Z. 152 (1924), pp. 309-345.Google Scholar
  7. 7.
    Zeviani M, Spinazzola A and Carelli V. Nuclear genes in mitochondrial disorders. Curr. opin. genetics dev. 13 (2003), pp. 262-270.CrossRefGoogle Scholar
  8. 8.
    Zeviani, M and Di Donato S. Mitochondrial disorders. tGuarantors of Brain. 127 (2004), pp. 2153-2172.Google Scholar
  9. 9.
    Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rotig A and Jeunemaitre X. The R22X mutation of the SDHD gene in hereditary paragangiloma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am. J. Hum. Genet. 69 (2001), pp. 1186-1197.PubMedCrossRefGoogle Scholar
  10. 10.
    Saarialho-Kere U, Kerkla E, Jeskanen L, Hasan T, Pierce R, Starcher B, Raudasoja R, Ranki A, Oikarinen A and Vaalamo M. Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12) in actinic damage. J. Invest. Dermatol. 113 (1999), pp. 664-672.PubMedCrossRefGoogle Scholar
  11. 11.
    Karelina TV, Goldberg GI and Eisen AZ. Matrilysin (PUMP) correlates with dermal invasion during appendageal development and cutaneous neoplasia. J. Invest. Dermatol. 103 (1994), pp. 482-487.PubMedCrossRefGoogle Scholar
  12. 12.
    Vaalamo M, Kariniemi A-L, Shapiro SD and Saarialho-Kere U. Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration. J. Invest. Dermatol. 112 (1999), pp. 499-505.PubMedCrossRefGoogle Scholar
  13. 13.
    Bernard PS and Wittwer CT. Real-Time PCR technology for cancer diagnostics. Clin. Chem. 48 (2002), pp. 1178-1185.PubMedGoogle Scholar
  14. 14.
    Mocellin S, Rossi CR and Marincola FM. Quantitative Real-Time PCR in cancer research. Arch. Immunol. ther. Ex. 51 (2003), pp. 301-313.Google Scholar
  15. 15.
    Ashton KJ, Weinstein SR, Maguire DJ, and Griffiths LR. Molecular cytogenetic analysis of basal cell carcinoma DNA using comparative genomic hybridisation. J of Invest. Dermatol. 117, No. 3 (2001), pp. 683-686.CrossRefGoogle Scholar
  16. 16.
    Bertram JS. The molecular biology of cancer. Mol. Aspects Med. 21 (2001), pp. 167-223.CrossRefGoogle Scholar
  17. 17.
    Maguire, D.J., Lintell, N.A., McCabe, M., Griffiths, L.R. & Ashton, K.S. Genomic and phenomic correlations in the respiration of non- melanotic skin cancers. Advances in Experimental Medicine and Biology. 540 (2003), pp. 251-256.PubMedGoogle Scholar
  18. 18.
    Lintell N. A., Maguire, D. J., McCabe, M. & Griffiths, L.R. Focussing on genomic and phenomic correlations in the respiration of non-melanotic skin cancers. Advances in Experimental Medicine and Biology. 566 (2004), pp. 375-380.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • N.A. Lintell
    • 1
  • D.J. Maguire
    • 1
  • L.R. Griffiths
    • 2
  • M. McCabe
    • 1
  1. 1.School of Biomolecular and Biomedical ScienceGriffith UniversityQueensland 4111Australia
  2. 2.School of Medical ScienceGriffith UniversityQueensland 4111Australia

Personalised recommendations