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View the Table of Contents for the March 1 issue of Cancer Research
Page 1642
The HER2 gene plays an important role in the pathogenesis of some human cancers, and mutations have recently been reported in lung cancers. Shigematsu et al. demonstrated that most HER2 mutations were in-frame insertions targeting the identical corresponding region as did EGFR insertions and were significantly more frequent in tumors arising in never smokers and having adenocarcinoma histology. The remarkable similarities of the mutational spectrums of EGFR and HER2 genes in lung cancers suggest similar etiologic factors. While mutations in the KRAS gene also targeted tumors of adenocarcinoma histology, they were more frequent in smokers. Mutations in EGFR, HER2 and KRAS genes were never present together in individual tumors and cell lines, suggesting different pathways to lung cancer in smokers and never smokers.
Page 1678
The identification of stereotypic molecular signatures may identify subtypes of tumors that, while similar on a histologic basis, exhibit disparate clinical and biologic behavior. In order to identify clinically relevant molecular subtypes of glioblastoma, Nigro et al. analyzed 34 tumor specimens for DNA-based alterations by array-comparative genomic hybridization (array-CGH) and RNA-based changes using expression microarrays. Unsupervised analyses using each platform subclassified the tumors concordantly, suggesting that they represented robust molecular subtypes. The most common array-CGH abnormality, loss of chromosome 10, was associated with changes in expression across the genome, suggesting that chromosome 10 status (loss versus no loss) defines distinct classes of glioblastoma.
Page 1693
An evaluation of transcripts from oral cavity, larynx, pharynx and thyroid was performed by Reis et al. after the generation and analysis of some 200,000 ESTs. The work revealed new genes, new splicing isoforms and performed a comparative analysis of transcriptomes among the tissues. Genes putatively specific of some tumor sites were identified and may include markers for the identification of metastatic cells. The mapping of transcripts to genomic regions consistently associated with these malignancies offers attractive candidates for tumor markers and to understanding the molecular basis of the disease. Similar analysis is warranted for a number of other tumors for which large EST datasets are available.
Page 2018
Using a mouse model of multistage cervical carcinogenesis induced by the HPV16 oncogenes, Daniel et al. demonstrated the therapeutic potential of immunologically targeting the E7 oncoprotein. K14-HPV16 transgenic mice were shown to develop spontaneous E7 autoantibodies, and CD4 T cells proliferated upon E7 priming, indicative of immune responsiveness. Indeed, immune surveillance was revealed in crosses to CD4-null mice, where tumor burden was 10-fold higher. When mice with incipient carcinomas were immunized with a recombinant protein fusing E7 to a natural adjuvant, a bacterial heat shock protein, progression of cervical cancer was impaired, encouraging