Details

Autor(en) / Beteiligte

• Elledge, Steve
• Pavlova, Natasha
• Davoli, Teresa
• Solimini, Nicole

Titel

Genetic Approaches to Cancer

Ist Teil von

• The FASEB journal, 2013-04, Vol.27 (S1)

Erscheinungsjahr

2013

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Abstract only Breast cancer is a collection of diseases with distinct clinical behaviors and underlying genetic causes. We have searched genetically for genes that have cancer relevant phenotypes including genes that alter cellular proliferation, cellular transformation, cell survival, cellular senescence, and genes that are essential for the proliferation of cancer cells. We have approached this by the generation of libraries of shRNAs for loss of function experiments and libraries of ORFs for gain of function experiments. We will discuss these technologies and how they can be applied to the functional dissection of genes important for breast cancer. Using these new technologies we have identified new oncogenes and tumor suppressors. We find that tumor cells selectively delete negative growth regulators and suggest that the deletion of clusters of these genes may drive tumorigenesis by haploinsufficiency. These recurrent deletions also avoid deletion of one copy of many essential genes through haploinsufficiency. We put forward the Cancer Gene Island model that postulates that tumors select for hemizygous loss of islands of gene enriched in negative regulators of proliferation and depleted in essential genes to promote tumor cell proliferation through cumulative haploinsufficiency.