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Microarray analysis was used to bring a comprehensive insight into underlying molecular mechanisms and obtain a whole assessment of aberrant gene expression in nasopharyngeal carcinoma (NPC). Combined with microdissection, gene expression profiles in 23 NPCs and 10 nontumor nasopharyngeal epithelial tissue samples were analyzed. Gene expression patterns suggested the dysregulation of the GTP/GDP-bound Ras cycle and an abnormal hyperactivity of cell cycle in NPC. Alterations in the WNT pathway suggest that this pathway may be activated in NPC. A 6-feature weighted-voting model was chosen because it represented the main characteristics of NPCs and predicted NPCs most accurately from the nontumor tissues (33 of 34 correct calls; 97.1% accuracy, Fisher’s exact test, P value = 8.389 × 10−8). The data generated in this study represent a comprehensive list of genes aberrantly regulated in NPC. The 6-feature weighted-voting model may provide an extensive list of potential molecular markers for early diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To clone the putative tumor suppressor gene(s) in a refined region at 9p21–22 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). Methods: We systematically screened the expression patterns of 25 novel ESTs (expressed sequence tags) in a minimal common deleted region of 9p21–22 in NPC. One of these ESTs was found down-regulated in NPC. Subsequently, the corresponding gene sequence of this EST was established by cDNA cloning and RACE (rapid amplification of cDNA end) procedures. Furthermore, a mouse homologue of this gene was identified. The expression of this gene was examined using Northern blot or reverse transcription-polymerase chain reaction (RT-PCR) in various human and mouse tissues. A limited screen for mutation of coding sequence of this novel human gene was undertaken using RT-PCR and direct sequencing analysis. Results: A novel gene was cloned. This gene is a new member of the UBA domain family, so we named it UBAP1 for ubiquitin-associated protein 1 (HUGO Gene Nomenclature Committee-approved symbol). Northern blot and RT-PCR analysis demonstrate a ubiquitous pattern of gene expression in human and mouse tissues. The direct sequencing analysis of the coding region of hUBAP1 following RT-PCR failed to reveal any mutations in a preliminary screen of NPC cell line HNE1 and primary nasopharyngeal carcinoma samples. Conclusions: We cloned a novel gene UBAP1, which is highly conserved between human and mouse. Clearly, as a novel member of UBA domain protein family and taking its map location into account, a more extensive analysis is essential to establish whether subtle mutations are present in nasopharyngeal carcinomas. [ABSTRACT FROM AUTHOR]