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

• DOI: 10.1016/j.celrep.2019.12.048
• Publication Date: 2020-01-14T22:15:44Z
• Authors: Jesus García-López; Kirby Wallace; Joel H. Otero; Rachelle Olsen; Yong-dong Wang; David Finkelstein; Brian L. Gudenas; Jerold E. Rehg; Paul Northcott; Andrew M. Davidoff; Kevin W. Freeman
• Keywords: ARID1A

Loss of heterozygosity (LOH) at 1p36 occurs in multiple cancers, including neuroblastoma (NBL). MYCN amplification and deletions tightly correlate with markers tumor aggressiveness NBL. Although distal losses associate single-copy tumors, larger amplification, indicating two suppressor regions 1p36, only one which facilitates oncogenesis. To better define this region, we genome-edited the syntenic locus primary mouse neural crest cells (NCCs), a putative NBL cell origin. In vitro transformation assays, show that Chd5 loss confers most MYCN-independent effects LOH. contrast, MYCN-driven tumorigenesis selects for NCCs Arid1a from pool randomly sized deletions, establishing as MYCN-associated suppressor. Our findings reveal collaborates oncogenic functions LOH