MPC Member Publications

This database contains a listing of population studies publications written by MPC Members. Anyone can add a publication by an MPC student, faculty, or staff member to this database; new citations will be reviewed and approved by MPC administrators.

Full Citation

Title: Imprinting defects at human 14q32 locus alters gene expression and is associated with the pathobiology of osteosarcoma

Citation Type: Book, Whole

Publication Year: 2014

ISBN: 1949-2553 (Electronic)\r1949-2553 (Linking)

ISSN: 1949-2553

DOI: 10.18632/oncotarget.6965

PMID: 26802029

Abstract: Osteosarcoma is the most common primary bone malignancy affecting children and adolescents. Although several genetic predisposing conditions have been associated with osteosarcoma, our understanding of its pathobiology is rather limited. Here we show that, first, an imprinting defect at human 14q32-locus is highly prevalent (87%) and specifically associated with osteosarcoma patients < 30 years of age. Second, the average demethylation at differentially methylated regions (DMRs) in the 14q32-locus varied significantly compared to genome-wide demethylation. Third, the 14q32-locus was enriched in both H3K4-me3 and H3K27-me3 histone modifications that affected expression of all imprinted genes and miRNAs in this region. Fourth, imprinting defects at 14q32 - DMRs are present in triad DNA samples from affected children and their biological parents. Finally, imprinting defects at 14q32-DMRs were also observed at higher frequencies in an Rb1/Trp53 mutationinduced osteosarcoma mouse model. Further analysis of normal and tumor tissues from a Sleeping Beauty mouse model of spontaneous osteosarcoma supported the notion that these imprinting defects may be a key factor in osteosarcoma pathobiology. In conclusion, we demonstrate that imprinting defects at the 14q32 locus significantly alter gene expression, may contribute to the pathogenesis of osteosarcoma, and could be predictive of survival outcomes.

Url: http://www.oncotarget.com/abstract/6965

User Submitted?: No

Authors: Shu, Jingmin; Li, Lihua; Sarver, Anne E.; Pope, Emily A; Varshney, Jyotika; Thayanithy, Venugopal; Spector, Logan G.; Largaespada, David; Clifford, J

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Publisher Location:

Pages: 21298-21314

Volume: 7

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IPUMS NHGIS NAPP IHIS ATUS Terrapop