Molecular Biology and Genetics of Cancer

  • Alberto Gulino
Part of the Updates in Surgery book series (UPDATESSURG)


The concept that cancer is a multi-step process caused by genetically- and epigenetically-determined abnormal gene function is now well established. Gain-of-function or loss-of-function changes affect a number of genes that control cellular processes such as cell cycle, apoptosis and differentiation and that consequently behave as oncogenes or tumor suppressors, respectively. It is also well established that several genetic hits are required to trigger cell transformation and malignant progression of cancer, in which the altered functions of each oncogene or tumor suppressor contribute, in a coordinated way, to compose the complex network of the cancer phenotypic traits [1, 2]. Elucidating how such gene function diversity is generated during the tumorigenic events is an unanswered question. Although tremendous advances in knowledge have occurred in recent years, there is still no clear understanding in this field.


Cancer Stem Cell Hedgehog Signaling Asymmetric Cell Division Cancer Gene Therapy Hedgehog Pathway 
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.
    Hahn WC, Weinberg RA (2002) Modelling the molecular circuitry of cancer. Nat Rev Cancer 2(5):331–341PubMedCrossRefGoogle Scholar
  2. 2.
    Chin L, Gray JW (2008) Translating insights from the cancer genome into clinical practice. Nature 452(7187):553–563PubMedCrossRefGoogle Scholar
  3. 3.
    Giannini G, Ristori E, Cerignoli F et al (2002) Human MRE11 is inactivated in mismatch repair-deficient cancers. EMBO Rep 3(3):248–254PubMedCrossRefGoogle Scholar
  4. 4.
    Capalbo C, Buffone A, Vestri A et al (2007) Does the search for large genomic rearrangements impact BRCAPRO carrier prediction? J Clin Oncol 25(18):2632–2634PubMedCrossRefGoogle Scholar
  5. 5.
    Palma M, Ristori E, Ricevuto E et al (2006) BRCA1 and BRCA2: the genetic testing and the current management options for mutation carriers. Crit Rev Oncol Hematol 57(1): 1–23PubMedCrossRefGoogle Scholar
  6. 6.
    Minucci S, Pelicci PG (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6:38–51PubMedCrossRefGoogle Scholar
  7. 7.
    Tacconelli A, Farina AR, Cappabianca L et al (2004) TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell 6(4):347–360PubMedCrossRefGoogle Scholar
  8. 8.
    Ferretti E, Di Marcotullio L, Gessi M et al (2006) Alternative splicing of the ErbB-4 cyto-plasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets. Oncogene 25(55):7267–7273PubMedCrossRefGoogle Scholar
  9. 9.
    Bellavia D, Mecarozzi M, Campese AF et al (2007) Notch3 and the Notch3-upregulated RNA-binding protein HuD regulate Ikaros alternative splicing. EMBO J.; 26(6): 1670–1680PubMedCrossRefGoogle Scholar
  10. 10.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866PubMedCrossRefGoogle Scholar
  11. 11.
    Laneve P, Di Marcotullio L, Gioia U et al (2007) The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells. Proc Natl Acad Sci U S A 104:7957–7962PubMedCrossRefGoogle Scholar
  12. 12.
    Ruiz i Altaba A (2006) Hedgehog-Gli signaling in human diseases. Ed Landes Bioscience, Kluwer Academic/Plenum Publishers, New YorkGoogle Scholar
  13. 13.
    Ferretti E, De Smaele E, Di Marcotullio L et al (2005) Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm. Trends Mol Med 11(12):537–545PubMedCrossRefGoogle Scholar
  14. 14.
    Thompson MC, Fuller C, Hogg TL et al (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924–1931PubMedCrossRefGoogle Scholar
  15. 15.
    Gallo R, Zazzeroni F, Alesse E et al (2002) REN: a novel, developmentally regulated gene that promotes neural cell differentiation. J Cell Biol 158(4):731–740PubMedCrossRefGoogle Scholar
  16. 16.
    Argenti B, Gallo R, Di Marcotullio L et al (2005) Hedgehog antagonist REN(KCTD11) regulates proliferation and apoptosis of developing granule cell progenitors. J Neurosci 25(36):8338–8346PubMedCrossRefGoogle Scholar
  17. 17.
    Di Marcotullio L, Ferretti E, De Smaele E et al (2004) REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma. Proc Natl Acad Sci USA 101(29): 10833–10838PubMedCrossRefGoogle Scholar
  18. 18.
    Di Marcotullio L, Ferretti E, De Smaele E et al (2006) Suppressors of hedgehog signaling: Linking aberrant development of neural progenitors and tumorigenesis. Mol Neurobiol 34(3): 193–204PubMedCrossRefGoogle Scholar
  19. 19.
    Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401PubMedCrossRefGoogle Scholar
  20. 20.
    Di Marcotullio L, Ferretti E, Greco A et al (2006) Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Nat Cell Biol 8(12): 1415–1423PubMedCrossRefGoogle Scholar
  21. 21.
    Di Marcotullio L, Ferretti E, Greco A et al (2007) Multiple ubiquitin-dependent processing pathways regulate hedgehog/gli signaling: implications for cell development and tumorigenesis. Cell Cycle 6(4):390–393PubMedGoogle Scholar
  22. 22.
    Klein AL, Zilian O, Suter U, Taylor V (2004) Murine numb regulates granule cell maturation in the cerebellum. Dev Biol 266(1): 161–177PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2009

Authors and Affiliations

  • Alberto Gulino
    • 1
  1. 1.Department of Experimental MedicineUniversity of Rome “La Sapienza”RomeItaly

Personalised recommendations