Lineage dependency and lineage-survival oncogenes in human cancer.
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.
Garraway
Levi A
LA
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. levi_garraway@dfci.harvard.edu
Sellers
William R
WR
D019070:Cell Lineage / Q000235:genetics*; D006801:Humans; D051739:Microphthalmia-Associated Transcription Factor / Q000502:physiology; D009369:Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins / Q000502:physiology; D009857:Oncogenes / Q000235:genetics*
C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D015513:Oncogene Proteins; C507278:survival-related gene product, human