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Translational aspects of the common 14q13 amplicon in human lung cancer
Author(s) -
Mu David,
Hsu David S.,
Acharya Chaitanya R.,
Riedel Richard F.,
Potti Anil
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb339
Subject(s) - lung cancer , amplicon , cancer research , gene , biology , cancer , transcription factor , bioinformatics , medicine , genetics , oncology , polymerase chain reaction
Previously we discovered and characterized the second most common amplicon in lung cancer, located at chromosomal region 14q13 and harboring three transcription factor genes ‐ TTF1, NKX2‐8, and PAX9. We showed that these three genes work in various combinations to cause malignant transformation (Kendall et al. 2007 PNAS 104: 16663). To further explore the clinical relevance of the three coamplified oncogenes, using stable transfectants of human bronchial epithelial cells we determined the RNA expression signatures that represent activation of the biological pathway defined by each of the three genes. By risk stratifying a non‐small cell lung cancer clinical dataset with the expression signatures, we discovered that co‐activation of TTF1 and NKX2‐8 pathways identified a cluster of patients (20%) with poor survival. We demonstrated that poor patient survival may be a reflection of resistance to platinum compounds, the standard care of lung cancer. Finally, we provide evidence that lung cancer cells with activated TTF1/NKX2‐8 pathways are sensitive to a RAS pathway inhibitor, providing a blueprint for future research regarding the treatment strategy of such type of lung cancer.