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A Putative Oncogenic Role for MPP11 in Head and Neck Squamous Cell Cancer¹

Departments of Molecular Biology and Genetics [V. A. R.], Otolaryngology-Head and Neck Surgery [V. A. R., O. C., M. R. B., W. H. W., L. W., J. J., D. S.], Pathology [W. H. W.], and Oncology [J. J., D. S.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195; Department of Molecular Pharmacology, Stanford School of Medicine, Palo Alto, California 94305 [J. M. W.]; and Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, V5Z 4H4 Canada [P. H.]

Genetic alterations of chromosome 7 are common in human cancer. Furthermore, previous studies have supported the presence of a gene important in a broad range of cancers at 7q22–31.1. There is evidence that supports an oncogenic function for this putative gene, as well as evidence that supports a tumor suppressive role. In this study, we used a cross-species candidate gene approach in combination with physical mapping to identify MPP11 as a candidate for the putative cancer-related activity at 7q22–31.1. We then analyzed primary head and neck squamous cell tumors (HNSCCs) for loss of heterozygosity/allelic imbalance (LOH/AI) at the MPP11 genomic locus. Thirty-eight percent of tumors examined displayed LOH/AI involving the MPP11 genomic locus. Mutation analysis of MPP11 in the latter samples did not identify any inactivating mutations. However, immunohistochemical staining of primary tumor sections and Western blot analysis of HNSCC cell lines revealed a tumor-specific high level of expression of MPP11p. Fluorescence in situ hybridization analysis done on the cell lines identified increased chromosome 7 copy number with a concomitant increase in MPP11 copy number. These results suggest an oncogenic role for MPP11 in HNSCC.

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