Large 1p36 Deletions Affecting Arid1a Locus Facilitate Mycn-Driven Oncogenesis in Neuroblastoma.

Autor:	García-López J; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: jesus.garcialopez@stjude.org., Wallace K; Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Genetics, Genomics & Informatics, The University of Tennessee Health Science Center (UTHSC), Memphis, TN 38103, USA., Otero JH; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Olsen R; Department of Oncological Sciences, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA., Wang YD; Computational Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Finkelstein D; Computational Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Gudenas BL; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA., Rehg JE; Pathology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Northcott P; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA., Davidoff AM; Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Freeman KW; Genetics, Genomics & Informatics, The University of Tennessee Health Science Center (UTHSC), Memphis, TN 38103, USA. Electronic address: kfreem22@uthsc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Jan 14; Vol. 30 (2), pp. 454-464.e5.
DOI:	10.1016/j.celrep.2019.12.048
Abstrakt:	Loss of heterozygosity (LOH) at 1p36 occurs in multiple cancers, including neuroblastoma (NBL). MYCN amplification and 1p36 deletions tightly correlate with markers of tumor aggressiveness in NBL. Although distal 1p36 losses associate with single-copy MYCN tumors, larger deletions correlate with MYCN amplification, indicating two tumor suppressor regions in 1p36, only one of which facilitates MYCN oncogenesis. To better define this region, we genome-edited the syntenic 1p36 locus in primary mouse neural crest cells (NCCs), a putative NBL cell of origin. In in vitro cell transformation assays, we show that Chd5 loss confers most of the MYCN-independent tumor suppressor effects of 1p36 LOH. In contrast, MYCN-driven tumorigenesis selects for NCCs with Arid1a deletions from a pool of NCCs with randomly sized 1p36 deletions, establishing Arid1a as the MYCN-associated tumor suppressor. Our findings reveal that Arid1a loss collaborates with oncogenic MYCN and better define the tumor suppressor functions of 1p36 LOH in NBL. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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