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BMC Genomics. 2016 Aug 22;17 Suppl 7:532. doi: 10.1186/s12864-016-2904-y.

Concordance of copy number loss and down-regulation of tumor suppressor genes: a pan-cancer study.

Zhao M1, Zhao Z2,3,4,5.

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School of Engineering, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD, 4558, Australia.
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, 37212, USA.
Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.



Tumor suppressor genes (TSGs) encode the guardian molecules to control cell growth. The genomic alteration of TSGs may cause tumorigenesis and promote cancer progression. So far, investigators have mainly studied the functional effects of somatic single nucleotide variants in TSGs. Copy number variation (CNV) is another important form of genetic variation, and is often involved in cancer biology and drug treatment, but studies of CNV in TSGs are less represented in literature. In addition, there is a lack of a combinatory analysis of gene expression and CNV in this important gene set. Such a study may provide more insights into the relationship between gene dosage and tumorigenesis. To meet this demand, we performed a systematic analysis of CNVs and gene expression in TSGs to provide a systematic view of CNV and gene expression change in TSGs in pan-cancer.


We identified 1170 TSGs with copy number gain or loss in 5846 tumor samples. Among them, 207 TSGs tended to have copy number loss (CNL), from which fifteen CNL hotspot regions were identified. The functional enrichment analysis revealed that the 207 TSGs were enriched in cancer-related pathways such as P53 signaling pathway and the P53 interactome. We further performed integrative analyses of CNV with gene expression using the data from the matched tumor samples. We found 81 TSGs with concordant CNL events and decreased gene expression in the tumor samples we examined. Remarkably, seven TSGs displayed concordant CNL and gene down-regulation in at least 50 tumor samples: MTAP (212 samples), PTEN (139), MCPH1 (85), FBXO25 (67), SMAD4 (64), TRIM35 (57), and RB1 (54). Specifically to MTAP, this concordance was found in 14 cancer types, an observation that is not much reported in literature yet. Further network-based analysis revealed that these TSGs with concordant CNL and gene down-regulation were highly connected.


This study provides a draft landscape of CNV in pan-cancer. Our findings of systematic concordance between CNL and down-regulation of gene expression may help better understand the TSG biology in tumorigenesis and cancer progression.


Copy number loss; Copy number variation; Gene expression; Pan-cancer; Tumor suppressor gene

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