Molecular mechanisms of activating c-MET in KSHV+ primary effusion lymphoma
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Bao Quoc Lam1,2,*, Lu Dai1,2,3,*, Li Li2, Jing Qiao3, Zhen Lin4, Zhiqiang Qin1,2,3
1Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
2Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
3Department of Pediatrics, Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
4Department of Pathology, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA 70112, USA
*These authors have contributed equally to this work
Zhen Lin, email: firstname.lastname@example.org
Zhiqiang Qin, email: email@example.com
Keywords: KSHV, primary effusion lymphoma, c-MET, Plexin-B1, SNV
Received: December 06, 2016 Accepted: January 21, 2017 Published: February 17, 2017
The oncogenic Kaposi’s sarcoma–associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL), which is mostly seen in immunosuppressed patients. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated in PEL cells and represents a promising therapeutic target (Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET activation within PEL cells remain largely unknown. To solve this puzzle, here we have utilized the next generation sequencing (NGS) based bioinformatics approach to investigate the genomic landscape of the c-MET gene and we found that there’s no single nucleotide variations (SNVs) occurred in the c-MET genomic regions in a cohort of PEL samples. Consistently, Sanger sequencing analysis of frequently mutated exons such as exon 10, 14 and 19 shows no mutation of these c-MET exons in PEL cell-lines, which further supports the notion that mutations are not the major mechanism responsible for c-MET activation in PEL. Further, we found that a transmembrane receptor protein, Plexin-B1, is expressed in PEL cell-lines, which is required for c-MET-mediated PEL cell survival via direct protein interaction.
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