Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

To date, the only entire Epstein-Barr virus (EBV) genomic sequence available in the database is the prototype B95.8, which was derived from an individual with infectious mononucleosis. A causative link between EBV and nasopharyngeal carcinoma (NPC), a disease with a distinctly high incidence in southern China, has been widely investigated. However, no full-length analysis of any substrain of EBV from this area has been reported. In this study, we analyzed the entire genomic sequence of an EBV strain from a patient with NPC in Guangdong, China. This EBV strain was termed GD1 (Guangdong strain 1), and the full-length sequence of GD1 was submitted to the GenBank database. The assigned accession number is AY961628. The entire GD1 sequence is 171,656 bp in length, with 59.5% G؉C content and 40.5% A؉T content. We detected many sequence variations in GD1 compared to prototypical strain B95.8, including 43 deletion sites, 44 insertion sites, and 1,413 point mutations. Furthermore, we evaluated the frequency of some of these GD1 mutations in Cantonese NPC patients and found them to be highly prevalent. These findings suggest that GD1 is highly representative of the EBV strains isolated from NPC patients in Guangdong, China, an area with the highest incidence of NPC in the world. Furthermore, these findings provide the second full-length sequence analysis of any EBV strain as well as the first full-length sequence analysis of an NPC-derived EBV strain.

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Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.

Background: Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer. Methods: A co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model. Results: In this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncR-NAs (Z68871.

Transmembrane protein 88 (TMEM88) is a transmembrane protein that plays a crucial role in regulating human stem cell differentiation and embryonic development. However, its expression and clinicopathologic significance in human neoplasms is unclear. In this study, the expression and subcellular localizations of TMEM88 were assessed in 214 cases of non-small cell lung cancer (NSCLC). Notably, TMEM88 was highly expressed in the cytosol of $60% NSCLC specimens examined. Higher expression of cytosolic TMEM88 in NSCLC correlated significantly with poor differentiation, high TNM stage, lymph node metastasis, and inferior survival. In NSCLC cells displaying membrane-localized TMEM88, we observed an inhibition of canonical Wnt signaling due to interactions of TMEM88 with the Wnt pathway factor Dishevelled (DVLS). In contrast, NSCLC cells with cytosol-localized TMEM88 lacked effects on Wnt signaling. Cytosolic interactions of TMEM88 and DVLS increased the expression of phosphorylated, active forms of p38, GSK3b (Thr390), and Snail, thereby reducing the expression of the tight junction-associated proteins ZO-1 and occludin, effects associated with enhanced invasive and metastatic cell characters. Importantly, attenuating the expression of cytosolic TMEM88 reduced metastatic prowess in xenograft models. Overall, our findings show how mislocalization of TMEM88 to the cytosol in NSCLC cells ablates its Wnt pathway regulatory properties, thereby promoting invasion and metastasis by activating the p38-GSK3b-Snail signaling pathway. Cancer Res; 75(21); 4527-37. Ó2015 AACR.

BACKGROUNDPrevious studies have suggested that genetic susceptibility may play an important role in the etiology of nasopharyngeal cancer (NPC). However, to date, few large‐scale studies have been conducted on familial risk and clustering of NPC in a high‐risk area of China.METHODSIn the current study, 2252 patients with NPC who were treated at the Cancer Center of Sun Yat‐Sen University in Guangdong Province, China, were identified as probands. Family histories of NPC and other malignancies were observed in first‐degree relatives (FDRs) and second‐degree relatives, and other information was obtained through interviews. One thousand nine hundred and three Cantonese families were selected for further investigation. To assess familial aggregation, the authors used standardized incidence ratios (SIRs) to measure the risk of NPC for FDRs and compared the observed number of cases with the number predicted by population‐based frequencies in the Cantonese population of Hong Kong.RESULTSThe current analysis indicated that families with ≥ 3 relatives who had NPC were distributed predominantly among a high‐risk subgroup of the Cantonese population in Guangdong Province and that the frequency of these families was 0.68%. An SIR of 2.09 (95% confidence interval [CI], 1.80–2.40) was observed among 13,833 FDRs in the high‐risk subgroup, and a significantly elevated risk for NPC was observed in FDRs of probands with early age of onset (age < 40 years; SIR, 9.01 [95% CI, 6.10–13.30]). Furthermore, decreased risks of hepatic, lung, esophageal, gastric, and breast carcinoma, as well as malignancy of all sites, were observed among FDRs of probands with NPC when Hong Kong and Shanghai populations were used as reference groups.CONCLUSIONSNPC tends to aggregate in Cantonese families in Guangdong Province, and the malignancies in these families appear to be site specific, with no excess of any other malignancy. Cancer 2004. © 2004 American Cancer Society.

Invasion and migration is the hallmark of malignant tumors as well as the major cause for breast cancer death. The polypyrimidine tract binding, PTB, protein serves as an important model for understanding how RNA binding proteins affect proliferation and invasion and how changes in the expression of these proteins can control complex programs of tumorigenesis. We have investigated some roles of polypyrimidine tract binding protein 1 (PTBP1) in human breast cancer. We found that PTBP1 was upregulated in breast cancer tissues compared with normal tissues and the same result was confirmed in breast cancer cell lines. Knockdown of PTBP1 substantially inhibited tumor cell growth, migration, and invasion. These results suggest that PTBP1 is associated with breast tumorigenesis and appears to be required for tumor cell growth and maintenance of metastasis. We further analyzed the relationship between PTBP1 and clinicopathological parameters and found that PTBP1 was correlated with her‐2 expression, lymph node metastasis, and pathological stage. This will be a novel target for her‐2(+) breast cancer. PTBP1 exerts these effects, in part, by regulating the phosphatase and tensin homolog‐phosphatidylinositol‐4,5‐bisphosphate 3‐kinase/protein kinase B (PTEN‐PI3K/Akt) pathway and autophagy, and consequently alters cell growth and contributes to the invasion and metastasis.