A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

Background

Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.

Methods

A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina^® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).

Results

Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (P_combined = 1.54x10^-5; odds ratio (OR) = 7.27; 95% CI = 2.96–17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (P_combined = 1.29x10^-3; OR = 4.21; 95% CI = 1.75–10.11) overlapping MICA/HCP5/HCG26 genes.

Conclusion

Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.     

Direction and viewing area-sensitive influence of EOG artifacts revealed in the EEG topographic pattern analysis

The influence of eye movement-related artifacts on electroencephalography (EEG) signals of human subjects, who were requested to perform a direction or viewing area dependent saccade task, was investigated by using a simultaneous recording with ocular potentials as electro-oculography (EOG). In the past, EOG artifact removals have been studied in tasks with a single fixation point in the screen center, with less attention to the sensitivity of cornea-retinal dipole orientations to the EEG head map. In the present study, we hypothesized the existence of a systematic EOG influence that differs according to coupling conditions of eye-movement directions with viewing areas including different fixation points. The effect was validated in the linear regression analysis by using 12 task conditions combining horizontal/vertical eye-movement direction and three segregated zones of gaze in the screen. In the first place, event-related potential topographic patterns were analyzed to compare the 12 conditions and propagation coefficients of the linear regression analysis were successively calculated in each condition. As a result, the EOG influences were significantly different in a large number of EEG channels, especially in the case of horizontal eye-movements. In the cross validation, the linear regression analysis using the appropriate dataset of the target direction/viewing area combination demonstrated an improved performance compared with the traditional methods using a single fixation at the center. This result may open a potential way to improve artifact correction methods by considering the systematic EOG influence that can be predicted according to the view angle such as using eye-tracker systems.     

Cancer stem cells: A review from origin to therapeutic implications

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment.     

Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota

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