Molecular epidemiology of hepatitis E virus in Hong Kong.

Hepatitis E virus (HEV) is one of the major causes of acute and self-limiting hepatitis in human. In Hong Kong, the number of notifications increased from 26 to 62 from year 2001 to 2007. This study describes the molecular epidemiology of HEV in Hong Kong in order to determine the movement and distribution of HEV. HEV in 171 serum samples from HEV IgM positive cases from year 2001 to 2007 were amplified using RT-PCR and subjected to nucleotide sequencing. Phylogenetic analysis showed 162 of 171 HEV detected cases (94.7%) belonged to genotype IV and 8 (4.7%) to genotype I. Interestingly, a cluster of 10 cases in year 2007 that had the same sequence of HEV was identified. Epidemiological data however did not detect any relationship between these cases. Since zoonotic transmission is a well known route of HEV infection, close monitoring of the circulating HEV strains in human and food source animals may help to provide additional information on the transmission of HEV and possible source of infection in Hong Kong.

High-throughput loss-of-heterozygosity study of chromosome 3p in lung cancer using single-nucleotide polymorphism markers.

Loss of DNA copy number at the short arm of chromosome 3 is one of the most common genetic changes in human lung cancer, suggesting the existence of one or more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted regions and candidate TSGs within these regions, a recently developed single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was applied to investigate the loss of heterozygosity (LOH) in 30 primary non-small-cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at 3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker distance in the present study is approximately 180 kb. Several frequently deleted regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several candidate TSGs within these frequently detected LOH regions have been found, including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study also showed that SMSG technology is a very useful approach to rapidly define the minimal deleted region and to identify target TSGs in a given cancer.

Co-overexpression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinoma.

BACKGROUND: Lung cancer is a prevalent cancer with a poor prognosis. To develop a useful in vitro cell model, a cell line of lung squamous cell carcinoma (SCC-35) was established. METHODS: The SCC-35 cell was characterized by comparative genomic hybridization (CGH) and spectral karyotyping (SKY). Chromosome microdissection, fluorescence in situ hybridization (FISH), and Southern and Northern blots analyses were used to study target genes. RESULTS: Two amplicons were found at chromosomes 7p12 and 11q13. Amplification and overexpression of epidermal growth factor receptor (EGFR) at 7p12 and fibroblast growth factor 3 (FGF3) at 11q13 were found. To understand the correlation between these two genes in nonsmall cell lung carcinoma (NSCLC) more comprehensively, overexpression of FGF3 and EGFR was investigated by immunohistochemistry with a tissue microarray containing 406 NSCLC samples. Cytoplasmic overexpression of FGF3 and EGFR was detected in 61% and 69% NSCLC cases, respectively. More interestingly, a significant correlation between overexpression of FGF3 and EGFR was found in NSCLC. CONCLUSION: These results suggest that co-overexpression of FGF3 and EGFR may play an important role in the pathogenesis of lung carcinoma.

Characterization of 3p, 5p, and 3q in two nasopharyngeal carcinoma cell lines, using region-specific multiplex fluorescence in situ hybridization probes.

Amplification of chromosome arms 3q and 5p and deletion of 3p were frequently detected in nasopharyngeal carcinoma (NPC) with comparative genomic hybridization and loss of heterozygosity studies. To identify the minimal amplified or deleted regions in these arms, structural aberrations in chromosome arms 3p, 3q, and 5p in two NPC cell lines, CNE1 and SUNE1, were studied with multiplex-color FISH (M-FISH) and chromosome region-specific probes (CRP). All CRPs, which were generated from microdissected DNA, were specific and strong in intensity, and sensitive enough to detect chromosome aberrations including translocations, deletions, and amplifications of target regions. In these two NPC cell lines, minimal regions of deletion and amplification were found at 3p12 and 3q26 approximately q27, respectively. On 5p, most of the regions were amplified as intact copies. Interregion translocations of these three arms were also observed. The amplification on 3q26 approximately q27 provided useful hints for further screening the minimal amplification at RP11-115J24 (3q26.2), containing candidate oncogene eIF-5A2. M-FISH with CRPs is thus not only useful in revealing a comprehensive picture of structural aberrations in target chromosomes, but also in narrowing down the minimal region for screening cancer-related genes.

Recurrent chromosomal imbalances in nonsmall cell lung carcinoma: the association between 1q amplification and tumor recurrence.

BACKGROUND: Lung carcinoma is a leading cause of cancer deaths worldwide. To better understand this disease, the authors studied genetic alterations in nonsmall cell lung carcinoma (NSCLC) and the association between genetic changes and clinical features. METHODS: Genetic alterations in 30 patients with adenocarcinoma (AC) and 39 patients with squamous cell carcinoma (SCC) were analyzed by comparative genomic hybridization. The genetic changes in patients with AC and SCC were compared and the associations of these changes with clinical features were studied. RESULTS: A gain of 3q with a minimal amplified region at 3q25.3-qter was significantly higher in patients with SCC compared with patients with AC (72% vs. 27%; P < 0.001). A gain of 20q and loss of chromosome 9 were detected more frequently in patients with AC compared with patients with SCC (P < 0.05). Gains of 5p and 20q and loss of 5q were significantly correlated with an advanced stage of NSCLC (P < 0.05). Amplification of 1q was significantly associated with NSCLC recurrence (P = 0.04). CONCLUSIONS: The results of the current study suggested that different chromosomal aberrations may contribute to the types and pathologic stages of NSCLC.