Lineage dependency and lineage-survival oncogenes in human cancer

Nat Rev Cancer. 2006 Aug;6(8):593-602. doi: 10.1038/nrc1947.


Although cell-lineage and differentiation models dominate tumour classification and treatment, the recognition that cancer is also a genomic disease has prompted a reconfiguration of cancer taxonomies according to molecular criteria. Recent evidence indicates that a synthesis of lineage-based and genetic paradigms might offer new insights into crucial and therapeutically pliable tumour dependencies. For example, MITF (microphthalmia-associated transcription factor), which is a master regulator of the melanocyte lineage, might become a melanoma oncogene when deregulated in certain genetic contexts. MITF and other lineage-survival genes therefore implicate lineage dependency (or lineage addiction) as a newly recognized mechanism that is affected by tumour genetic alterations.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Lineage / genetics*
  • Humans
  • Microphthalmia-Associated Transcription Factor / physiology
  • Neoplasms / genetics*
  • Oncogene Proteins / physiology
  • Oncogenes / genetics*


  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Oncogene Proteins
  • survival-related gene product, human