CBL Is Frequently Altered in Lung Cancers: Its Relationship to Mutations in MET and EGFR Tyrosine Kinases

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CBL Is Frequently Altered in Lung Cancers: Its Relationship to Mutations in MET and EGFR Tyrosine Kinases

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Title: CBL Is Frequently Altered in Lung Cancers: Its Relationship to Mutations in MET and EGFR Tyrosine Kinases
Author: Tan, Yi-Hung Carol; Krishnaswamy, Soundararajan; Nandi, Suvobroto; Kanteti, Rajani; Vora, Sapana; Onel, Kenan; Hasina, Rifat; Lo, Fang-Yi; El-Hashani, Essam; Cervantes, Gustavo; Lipkowitz, Stanley; Karrison, Theodore; Vokes, Everett E.; Wang, Yi-Ching; Salgia, Ravi; Najbauer, Joseph; Robinson, Matthew; Kales, Stephen C.; Sattler, Martin

Note: Order does not necessarily reflect citation order of authors.

Citation: Tan, Yi-Hung Carol, Soundararajan Krishnaswamy, Suvobroto Nandi, Rajani Kanteti, Sapana Vora, Kenan Onel, Rifat Hasina, et al. 2010. CBL Is Frequently Altered in Lung Cancers: Its Relationship to Mutations in MET and EGFR Tyrosine Kinases. PLoS ONE 5(1): e8972.
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Abstract: Background: Non-small cell lung cancer (NSCLC) is a heterogeneous group of disorders with a number of genetic and proteomic alterations. c-CBL is an E3 ubiquitin ligase and adaptor molecule important in normal homeostasis and cancer. We determined the genetic variations of c-CBL, relationship to receptor tyrosine kinases (EGFR and MET), and functionality in NSCLC. Methods and Findings: Using archival formalin-fixed paraffin embedded (FFPE) extracted genomic DNA, we show that c-CBL mutations occur in somatic fashion for lung cancers. c-CBL mutations were not mutually exclusive of MET or EGFR mutations; however they were independent of p53 and KRAS mutations. In normal/tumor pairwise analysis, there was significant loss of heterozygosity (LOH) for the c-CBL locus (22%, n = 8/37) and none of these samples revealed any mutation in the remaining copy of c-CBL. The c-CBL LOH also positively correlated with EGFR and MET mutations observed in the same samples. Using select c-CBL somatic mutations such as S80N/H94Y, Q249E and W802* (obtained from Caucasian, Taiwanese and African-American samples, respectively) transfected in NSCLC cell lines, there was increased cell viability and cell motility. Conclusions: Taking the overall mutation rate of c-CBL to be a combination as somatic missense mutation and LOH, it is clear that c-CBL is highly mutated in lung cancers and may play an essential role in lung tumorigenesis and metastasis.
Published Version: doi://10.1371/journal.pone.0008972
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813301/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8000934

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