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Cancer Lett DOI:10.1016/j.canlet.2005.08.007

A transforming MET mutation discovered in non-small cell lung cancer using microarray-based resequencing.

Publication TypeJournal Article
Year of Publication2006
AuthorsTengs, T, Lee, JC, J Paez, G, Zhao, X, LaFramboise, T, Giannoukos, G, Thomas, RK
JournalCancer Lett
Date Published2006 Aug 08
KeywordsCarcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

We have designed resequencing microarrays to test the performance of this platform when interrogating a large number of exons (164 total) from genes associated with cancer. To evaluate false positive and negative rates, dideoxy sequencing was done for 335,420 bases interrogated by the arrays. From the array data, calls could be made for approximately 97.5% of the bases, and false positive rates were very low with only a single mutation reported from the array dataset for which the corresponding dideoxy trace had a clean wildtype sequence. For the nucleotide positions where array calls were made, false negative rates were 1.41% for heterozygous mutations. All the homozygous mutations were detected, but 8.11% were erroneously reported as heterozygous changes from the reference sequence by the array analysis software. In addition, 20 non-small cell lung cancer (NSCLC) samples were analyzed using the arrays, and both somatic and germline mutations were found. The most interesting findings were two MET mutations that have recently been implemented in NSCLC. Large scale MALDI-TOF genotyping indicated that one of these mutations (T1010I) might represent a true cancer-causing genotype, whereas the other (N375S) appears to be a common germline polymorphism.


Alternate JournalCancer Lett.
PubMed ID16171945