Somatic alteration and depleted nuclear expression of BAP1 in human esophageal squamous cell carcinoma

• DOI: 10.1111/cas.12722
• Publication Date: 2015-06-17T08:35:51Z
• Authors: Takahiro Mori; Makiko Sumii; Fumiyoshi Fujishima; Kazuko Ueno; Mitsuru Emi; Masao Nagasaki; Chikashi Ishioka; Natsuko Chiba
• Keywords: BAP1; Deubiquitinating enzyme; Wild type

BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that involved in the regulation of cell growth. Recently, many somatic and germline mutations BAP1 have been reported broad spectrum tumors. In this study, we identified novel non-synonymous mutation, phenylalanine-to-isoleucine substitution at codon 170 (F170I), 49 patients with esophageal squamous carcinoma (ESCC). Multiplex ligation-dependent probe amplification (MLPA) gene ESCC tumor disclosed monoallelic deletion (LOH), suggesting alterations on both alleles tumor. The deubiquitinase activity auto-deubiquitinase F170I-mutant were markedly suppressed compared wild-type BAP1. addition, mostly localizes to nucleus, whereas F170I mutant preferentially localized cytoplasm. Microarray analysis revealed expression drastically altered profiles expressed Gene-ontology analyses indicated mutation genes oncogenic pathways. We found one candidate, TCEAL7, previously as putative suppressor gene, was significantly induced by Furthermore, level nucleus reduced 44% examined immunohistochemistry (IHC). Because nuclear localization important for its function, may be functionally inactivated substantial portion ESCC. Taken together, likely function least part