Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer.

摘要: Increased copy number involving chromosome 3q26 is a frequent and early event in cancers of the ovary, lung, head neck, cervix, BRCA1 positive basal breast cancers. The p110alpha catalytic subunit phosphoinositide-3-kinase (PI3KCA) protein kinase Ciota (PKCiota) have previously been shown as functionally deregulated by 3q increase. High-resolution array comparative genomic hybridization 235 high-grade serous epithelial ovarian using contiguous bacterial artificial chromosomes across delineated an approximately 2 Mb-wide region at 3q26.2 encompassing PDCD10 to MYNN (chr3:168722613-170908630). Ecotropic viral integration site-1 (EVI1) myelodysplastic syndrome 1 (MDS1) are located center this region, their DNA increases associated with least 5-fold increased RNA transcript levels 83% 98% advanced cancers, respectively. Moreover, MDS1/EVI1 EVI1 cancer cell lines. gene products proliferation, migration, decreased transforming growth factor-beta-mediated plasminogen activator inhibitor-1 promoter activity cells. Intriguingly, transcripts improved patient outcomes, whereas poor survival. Thus, favorable prognosis seems be result high-level expression fusion MDS1/EVI1. Collectively, these studies suggest that EVI1, implicated acute myelogenous leukemia, contribute pathophysiology cancer.