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bioRxiv · 10.1101/353391

Genome-wide CNV study and functional evaluation identified CTDSPL as tumour suppressor gene for cervical cancer

Chen, D.·Wang, S.·Li, Z.·Cui, T.·Chen, Y.·Song, J.·Magnusson, P. K.·Wang, H.·Zhang, D.·Gyllensten, U.
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Abstract

We have investigated copy number variations (CNVs) in relation to cervical cancer by analyzing 731,422 single-nucleotide polymorphisms (SNPs) in 1,034 cervical cancer cases and 3,948 controls, followed by replication in 1,396 cases and 1,057 controls. We found that a 6367bp deletion in intron 1 of the CTD small phosphatase like gene (CTDSPL) was associated with 2.54-fold increased risk of cervical cancer (odds ratio =2.54, 95% confidence interval =2.08-3.12, P=2.0x10-19). This CNV is one of the strongest genetic risk variants identified so far for cervical cancer. The deletion removes the binding sites of zinc finger protein 263, binding protein 2 and interferon regulatory factor 1, and hence downregulates the transcription of CTDSPL. HeLa cells expressing CTDSPL showed a significant decrease in colony-forming ability. Compared with control groups, mice injected with HeLa cells expressing CTDSPL exhibited a significant reduction in tumour volume. Furthermore, CTDSPL-depleted immortalized End1/E6E7 could form tumours in NOD-SCID mice.

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Chen, D., Wang, S., Li, Z., Cui, T., Chen, Y., Song, J., Magnusson, P. K., Wang, H., Zhang, D., Gyllensten, U.. 2018-06-22. Genome-wide CNV study and functional evaluation identified CTDSPL as tumour suppressor gene for cervical cancer. https://doi.org/10.1101/353391

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