Dergi makalesi Açık Erişim
Hu, Xiaozhou; Baytak, Esra; Li, Jinnan; Akman, Burcu; Okay, Kaan; Hu, Genfu; Scuto, Anna; Zhang, Wenyan; Kucuk, Can
Follicular lymphoma (FL) is a common type of indolent lymphoma that occasionally transforms to more aggressive B-cell lymphomas. These transformed follicular lymphomas (tFL) are often associated with chemoresistance whose mechanisms are currently unknown. REL, a proto-oncogene located on frequently amplified 2p16.1-p15 locus, promotes tumorigenesis in many cancer types through deregulation of the NF-KB pathway; however, its role in FL pathobiology or chemoresistance has not been addressed. Here, we evaluated REL gene copy number by q-PCR on FFPE FL tumor samples, and observed REL amplification in 30.4% of FL cases that was associated with weak elevation of transcript levels. PCR-Sanger analysis did not show any somatic mutation in FL tumors. In support of a marginal oncogenic role, a REL-transduced FL cell line was positively selected under limiting serum conditions. Interestingly, reanalysis of previously reported gene expression profiles revealed significant enrichment of DNA damage-induced repair and cell cycle arrest pathways in tFL tumors with high REL expression compared to those with low REL expression consistent with the critical role of c-REL in genotoxicity-induced NF-KB signaling, which was reported to lead to drug resistance. In addition to DNA damage repair genes such as ATM and BRCA1, anti-apoptotic BCL2 was significantly elevated in REL-high FL and tFL tumors. Altogether these data suggest that other genes located in amplified 2p16.1-p15 locus may have more oncogenic role in FL etiology; however, high REL expression may be useful as a predictive biomarker of response to immunochemotherapy, and inhibition of c-REL may potentially sensitize resistant FL or tFL cells to chemotherapy. (C) 2017 Elsevier Ltd. All rights reserved.
Dosya adı | Boyutu | |
---|---|---|
bib-cdc083f8-f00f-4092-aa93-e52a98c9ee23.txt
md5:fac5332ebe39e791580056a585a754c6 |
259 Bytes | İndir |
Görüntülenme | 22 |
İndirme | 6 |
Veri hacmi | 1.6 kB |
Tekil görüntülenme | 22 |
Tekil indirme | 6 |