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Title: Copy number profiling of chimeric knockout retinoblastoma mice : Shallow whole genome sequencing of biopsies from retinoblastoma tumors in chimeric murine knockout double mice (pRb-p130 and pRb-p107 knockouts) to identify secondary alterations that drive oncogenesis.      
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ID:
PRJEB15170
description:
Several murine retinoblastoma models have been generated by deleting the genes encoding for retinoblastoma susceptibility protein pRb and one of its family members p107 or p130. In Rb-/-p107-/- retinoblastomas, somatic copy number alterations (SCNAs) like Mdm2 amplification or Cdkn2a deletion targeting the p53-pathway occur, which is uncommon for human retinoblastoma. In our study, we determined SCNAs in retinoblastomas developing in Rb-/-p130-/- mice and compared this to murine Rb-/-p107-/- tumors and human tumors.Chimeric mice were made by injection of 129/Ola-derived Rb-/-p130-/- embryonic stem cells into wild type C57BL/6 blastocysts. SCNAs of retinoblastoma samples were determined by low-coverage (~0.5x) whole genome sequencing.In Rb-/-p130-/- tumors, SCNAs included gain of chromosomes 1 (3/23 tumors), 8 (1/23 tumors), 10 (1/23 tumors), 11 (2/23 tumors), and 12 (4/23 tumors), which could be mapped to frequently altered chromosomes in human retinoblastomas. While the altered chromosomes in Rb-/-p130-/- tumors were similar to those in Rb-/-p107-/- tumors, the alteration frequencies were much lower in Rb-/-p130-/- tumors. Most of the Rb-/-p130-/- tumors (16/23 tumors, 70%) were devoid of SCNAs, in strong contrast to Rb-/-p107-/- tumors, which were never (0/15 tumors) SCNA-devoid. Similarly to human retinoblastoma, increased age at diagnosis significantly correlated with increased SCNA frequencies. Additionally, focal loss of Cdh11 was observed in one Rb-/-p130-/- tumor, which enforces studies in human retinoblastoma that identified CDH11 as a retinoblastoma suppressor. Moreover, based on a comparison of genes altered in human and murine retinoblastoma, we suggest exploring the role of HMGA1 and SRSF3 in retinoblastoma development.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJEB15170
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abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject