Chromosomal aberrations in nasopharyngeal carcinoma analyzed by comparative genomic hybridization

Chen, Yann Jang; Ko, Jen-Chung; Chen, Pei‐Jer; Shu, Chih Hung; Hsu, Ming; Tsai, Shih Feng; Lin, Chi

doi:10.1002/(sici)1098-2264(199906)25:2<169::aid-gcc13>3.0.co;2-i

Cited by 101 publications

(34 citation statements)

References 26 publications

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“…The gain of chromosome segment 17q21-q25 on 11p15 in immortalized NP460hTert apparently confers growth advantage to NP460hTert cells at the early stage of immortalization and facilitated its emergence from the first stage of immortalization. Gain of chromosome arm 17q21-q25 was also observed in nearly 40-50% of NPC samples by comparative genomic hybridization, 22 with the minimal overlapping regions at 17q21 and 17q25. Gain of chromosome 17 is commonly detected in other cancers.…”

Section: Discussionmentioning

confidence: 95%

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase

Man

Jin

et al. 2006

Intl Journal of Cancer

111

136

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Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase‐immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16INK4A locus and downregulation of RASSF1A expression. The deletion of the p16INK4A locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array‐based CGH revealed a gain of a 17q21‐q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16INK4A locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF‐κB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development. © 2006 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase

Man

Jin

et al. 2006

Intl Journal of Cancer

111

136

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“…Both are located at chromosome 17q11.2, a frequently amplified region in NPC. 31 Previous studies have reported that miR144/451 are abundant in blood cells and are important regulators of erythroid homeostasis. 32 miR144 also regulates nuclear factorerythroid 2-related factor 2, a key modulator of cellular response to oxidative stress in primary erythroid progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

Wong

Kong

Tsang

et al. 2011

Cancer

143

133

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BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERTþEBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. Cancer 2012;118:698-

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“…Out of 70 genes, six localise to 12p12 -13 (A2M, GAPDH, LPRP, CLECSF2, PRH, and EMP1), and three to 1q21 -22 (SPRR3, SPRR2, and S100A9). These are the two most frequently altered regions in nasopharyngeal carcinoma (Marenholz et al, 1996;Chen et al, 1999;Salomon-Nguyen et al, 2000;Sato et al, 2001), indicating that transformation has complex effects on epidermoid cell biology.…”

Section: Discussionmentioning

confidence: 99%

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC)

Lemaire

Millon²,

Young

et al. 2003

Br J Cancer

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Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780 000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a largescale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12 -13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.

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Chromosomal aberrations in nasopharyngeal carcinoma analyzed by comparative genomic hybridization

Cited by 101 publications

References 26 publications

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC)

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