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PLoS One. 2010 Jan 29;5(1):e8972. doi: 10.1371/journal.pone.0008972.

CBL is frequently altered in lung cancers: its relationship to mutations in MET and EGFR tyrosine kinases.

Author information

  • 1Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.

Erratum in

  • PLoS One. 2011;6(1). doi: 10.1371/annotation/940edb14-522e-4f38-b6c4-7557e9a13d15. Hsu, Han-Shui [added].

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.

PMID:
20126411
[PubMed - indexed for MEDLINE]
PMCID:
PMC2813301
Free PMC Article
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