Skip to main content
SpringerLink
Log in

Principles of Molecular Biology

  • Chapter
  • First Online:
Book cover Molecular Diagnostics in Dermatology and Dermatopathology

Part of the book series: Current Clinical Pathology ((CCPATH))

  • 1348 Accesses

Abstract

The rapid development of molecular biology in recent decades has dramatically changed the way we practice medicine. With the help of an impressive arsenal of new technologies, including high-throughput sequencing and microarrays, we are now well-equipped to probe into the molecular nature of diseases. Which set of genes are involved? What are the genetic and epigenetic alterations associated with these genes? In this chapter, we will describe the basic concepts of molecular biology, including genes, types of mutations, and gene expression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Watson JD, Crick FH. Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. Nature 1953;171:737–8. JAMA. 1993;269:1966–7.

    Google Scholar 

  2. Woese C. The genetic code. New York: Harper & Row; 1968.

    Google Scholar 

  3. Gilbert W. Origin of life: the RNA world. Nature. 1986;319:618.

    Article  Google Scholar 

  4. Claverie J-M. Gene number: what if there are only 30,000 human genes? Science. 2001;291:1255–7.

    Article  PubMed  CAS  Google Scholar 

  5. Belancio VP, Hedges DJ, Deininger P. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res. 2008;18:343–58.

    Article  PubMed  CAS  Google Scholar 

  6. Birney E, Stamatoyannopoulos JA, Dutta A, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447:799–816.

    Article  PubMed  CAS  Google Scholar 

  7. Harrington L. Does the reservoir for self-renewal stem from the ends? Oncogene. 2004;23:7283–9.

    Article  PubMed  CAS  Google Scholar 

  8. Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130:223–33.

    Article  PubMed  CAS  Google Scholar 

  9. Osterhage JL, Friedman KL. Chromosome end maintenance by telomerase. J Biol Chem. 2009;284:16061–5.

    Article  PubMed  CAS  Google Scholar 

  10. Muntoni A, Reddel RR. The first molecular details of ALT in human tumor cells. Hum Mol Genet. 2005;14 Suppl 2:R191–6.

    Article  PubMed  CAS  Google Scholar 

  11. Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88:557–79.

    Article  PubMed  CAS  Google Scholar 

  12. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6:611–22.

    Article  PubMed  CAS  Google Scholar 

  13. Flores I, Benetti R, Blasco MA. Telomerase regulation and stem cell behaviour. Curr Opin Cell Biol. 2006;18:254–60.

    Article  PubMed  CAS  Google Scholar 

  14. Mithani SK, Smith IM, Topalian SL, et al. Nonsynonymous somatic mitochondrial mutations occur in the majority of cutaneous melanomas. Melanoma Res. 2008;18:214–9.

    Article  PubMed  CAS  Google Scholar 

  15. Dakubo GD, Jakupciak JP, Birch-Machin MA, et al. Clinical implications and utility of field cancerization. Cancer Cell Int. 2007;7:2.

    Article  PubMed  Google Scholar 

  16. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448:83–6.

    Article  PubMed  CAS  Google Scholar 

  17. Mueller DW, Bosserhoff AK. Role of miRNAs in the progression of malignant melanoma. Br J Cancer. 2009;101:551–6.

    Article  PubMed  CAS  Google Scholar 

  18. Redon R, Ishikawa S, Fitch KR, et al. Global variation in copy number in the human genome. Nature. 2006;444:444–54.

    Article  PubMed  CAS  Google Scholar 

  19. Bosse Y, Bacot F, Montpetit A, et al. Identification of susceptibility genes for complex diseases using pooling-based genome-wide association scans. Hum Genet. 2009;125:305–18.

    Article  PubMed  Google Scholar 

  20. Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003;3:253–66.

    Article  PubMed  CAS  Google Scholar 

  21. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.

    Article  PubMed  CAS  Google Scholar 

  22. Millington GW. Epigenetics and dermatological disease. Pharmacogenomics. 2008;9:1835–50.

    Article  PubMed  CAS  Google Scholar 

  23. Knudson Jr AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68:820–3.

    Article  PubMed  Google Scholar 

  24. Garraway LA, Widlund HR, Rubin MA, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 2005;436:117–22.

    Article  PubMed  CAS  Google Scholar 

  25. Nielsen M, Kaltoft K, Nordahl M, et al. Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines. Proc Natl Acad Sci USA. 1997;94:6764–9.

    Article  PubMed  CAS  Google Scholar 

  26. Halaban R. Growth factors and melanomas. Semin Oncol. 1996;23:673–81.

    PubMed  CAS  Google Scholar 

  27. Beadling C, Jacobson-Dunlop E, Hodi FS, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008;14:6821–8.

    Article  PubMed  CAS  Google Scholar 

  28. Puri N, Ahmed S, Janamanchi V, et al. c-Met is a potentially new therapeutic target for treatment of human melanoma. Clin Cancer Res. 2007;13:2246–53.

    Article  PubMed  CAS  Google Scholar 

  29. Karbowniczek M, Spittle CS, Morrison T, et al. mTOR is activated in the majority of malignant melanomas. J Invest Dermatol. 2008;128:980–7.

    Article  PubMed  CAS  Google Scholar 

  30. Spencer JM, Kahn SM, Jiang W, et al. Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas. Arch Dermatol. 1995;131:796–800.

    Article  PubMed  CAS  Google Scholar 

  31. van der Schroeff JG, Evers LM, Boot AJ, et al. Ras oncogene mutations in basal cell carcinomas and squamous cell carcinomas of human skin. J Invest Dermatol. 1990;94:423–5.

    Article  PubMed  Google Scholar 

  32. Goldstein NB, Johannes WU, Gadeliya AV, et al. Active N-Ras and B-Raf inhibit anoikis by downregulating Bim expression in melanocytic cells. J Invest Dermatol. 2009;129:432–7.

    Article  PubMed  CAS  Google Scholar 

  33. Papp T, Pemsel H, Zimmermann R, et al. Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi. J Med Genet. 1999;36:610–4.

    PubMed  CAS  Google Scholar 

  34. van Dijk MC, Bernsen MR, Ruiter DJ. Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol. 2005;29:1145–51.

    Article  PubMed  Google Scholar 

  35. Pierceall WE, Goldberg LH, Tainsky MA, et al. Ras gene mutation and amplification in human nonmelanoma skin cancers. Mol Carcinog. 1991;4:196–202.

    Article  PubMed  CAS  Google Scholar 

  36. Thomas NE. BRAF somatic mutations in malignant melanoma and melanocytic naevi. Melanoma Res. 2006;16:97–103.

    Article  PubMed  CAS  Google Scholar 

  37. Meyle KD, Guldberg P. Genetic risk factors for melanoma. Hum Genet. 2009;126:499–510.

    Article  PubMed  CAS  Google Scholar 

  38. Lazarov M, Kubo Y, Cai T, et al. CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis. Nat Med. 2002;8:1105–14.

    Article  PubMed  CAS  Google Scholar 

  39. Sauter ER, Yeo UC, von Stemm A, et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res. 2002;62:3200–6.

    PubMed  CAS  Google Scholar 

  40. Eberle J, Hossini AM. Expression and function of bcl-2 proteins in melanoma. Curr Genomics. 2008;9:409–19.

    Article  PubMed  CAS  Google Scholar 

  41. Robertson GP. Functional and therapeutic significance of Akt deregulation in malignant melanoma. Cancer Metastasis Rev. 2005;24:273–85.

    Article  PubMed  CAS  Google Scholar 

  42. Delmas V, Beermann F, Martinozzi S, et al. Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev. 2007;21:2923–35.

    Article  PubMed  CAS  Google Scholar 

  43. Saldanha G, Ghura V, Potter L, et al. Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation. Br J Dermatol. 2004;151:157–64.

    Article  PubMed  CAS  Google Scholar 

  44. Reifenberger J, Wolter M, Knobbe CB, et al. Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. Br J Dermatol. 2005;152:43–51.

    Article  PubMed  CAS  Google Scholar 

  45. Nelson AA, Tsao H. Melanoma and genetics. Clin Dermatol. 2009;27:46–52.

    Article  PubMed  Google Scholar 

  46. Butani AK, Arbesfeld DM, Schwartz RA. Premalignant and early squamous cell carcinoma. Clin Plast Surg. 2005;32:223–35.

    Article  PubMed  Google Scholar 

  47. Navas IC, Algara P, Mateo M, et al. p16(INK4a) is selectively silenced in the tumoral progression of mycosis fungoides. Lab Invest. 2002;82:123–32.

    PubMed  CAS  Google Scholar 

  48. Kanellou P, Zaravinos A, Zioga M, et al. Genomic instability, mutations and expression analysis of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in actinic keratosis. Cancer Lett. 2008;264:145–61.

    Article  PubMed  CAS  Google Scholar 

  49. de Boer J, Hoeijmakers JH. Nucleotide excision repair and human syndromes. Carcinogenesis. 2000;21:453–60.

    Article  PubMed  Google Scholar 

  50. Rubben A, Bausch B, Nikkels A. Somatic deletion of the NF1 gene in a neurofibromatosis type 1-associated malignant melanoma demonstrated by digital PCR. Mol Cancer. 2006;5:36.

    Article  PubMed  Google Scholar 

  51. Bianchi AB, Hara T, Ramesh V, et al. Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet. 1994;6:185–92.

    Article  PubMed  CAS  Google Scholar 

  52. Zembowicz A, Knoepp SM, Bei T, et al. Loss of expression of protein kinase A regulatory subunit 1[alpha] in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions. Am J Surg Pathol. 2007;31:1764–75.

    Article  PubMed  Google Scholar 

  53. Katona TM, O’Malley DP, Cheng L, et al. Loss of heterozygosity analysis identifies genetic abnormalities in mycosis fungoides and specific loci associated with disease progression. Am J Surg Pathol. 2007;31:1552–6.

    Article  PubMed  Google Scholar 

  54. Adolphe C, Hetherington R, Ellis T, et al. Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res. 2006;66:2081–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, New York Medical College, Westchester Medical Center, 100 Woods Road, Valhalla, NY, 10505, USA

    Wenyong Zhang

Authors
  1. Jian Zhuge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenyong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wenyong Zhang .

Editor information

Editors and Affiliations

  1. Health Center, Dept. Dermatology, University of Connecticut, Farmington Ave. 263, Farmington, 06030, Connecticut, USA

    Michael J. Murphy

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Zhuge, J., Zhang, W. (2011). Principles of Molecular Biology. In: Murphy, M. (eds) Molecular Diagnostics in Dermatology and Dermatopathology. Current Clinical Pathology. Humana Press. https://doi.org/10.1007/978-1-60761-171-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-171-4_2

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-170-7

  • Online ISBN: 978-1-60761-171-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation