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5033330 
Technical Report 
Loss of PTEN as a Predictive Biomarker of REsponse to Lithium Chloride, a Potential Targeted Treatment for Breast Cancer 
Higgins, M 
2011 
GRA and I 
e 0 
The phosphatidylinositol 3-kinase (PI3K) pathway mediates key cellular functions, including growth, proliferation, survival and angiogenesis. The gene encoding the catalytic domain of PI3K, PIK3CA, has been found to be mutated in breast cancers at high frequency. The tumor suppressor PTEN reverses the effects of PI3K by dephosphorylating the same site on membrane phosphatidylinositols that is phosphorylated by PI3K. Genomic analysis of the PTEN gene has identified it as one of the most commonly mutated or deleted tumor suppressors in human malignancies. In breast cancer, genetic alterations of both PTEN alleles are found with a frequency of about 5%, however monoalleleic loss of PTEN is observed in as many as 50% of cases, and this can lead to aberrant PTEN signaling, resulting in early metastasis and poor prognosis.