IP6K2 predicts favorable clinical outcome of primary breast cancer

Sandström, Josefine; Balian, A.; Lockowandt, Rebecca; Fornander, Tommy; Nordenskjöld, Bo; Lindström, Linda S.; Pérez-Tenorio, Gizeh; Stål, Olle

doi:10.3892/mco.2021.2256

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…We examined the relationship between ASE and SCNAs for two genes, IP6K2 and KIF1B , which have been previously identified as potential tumor suppressors located within the chromosome 3p and 1p deletion regions. Knockdown of IP6K2 impairs apoptosis in colorectal cancer cells [ 45 ], and its deletion or low expression is associated with adverse clinical outcomes in aerodigestive tract carcinoma and breast cancer [ 46 , 47 ]. Overexpression of KIF1B in neuroblastoma cell lines causes apoptotic cell death and its knockdown enhances tumor formation in mouse models [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma

et al. 2022

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Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma.

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