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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2014

Open Access 01-12-2014 | Research

Identification of a novel gene fusion (BMX-ARHGAP) in gastric cardia adenocarcinoma

Authors: Xiaofeng Xu, Lifang Xu, Feng Gao, Jianjiang Wang, Jinsong Ye, Mingxian Zhou, Yunling Zhu, Lan Tao

Published in: Diagnostic Pathology | Issue 1/2014

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Abstract

Background

Gastric cardia adenocarcinoma (GCA) is one of the major causes of cancer related mortality worldwide. We aim to provide new understanding in the pathogenesis of GCA through investigations on gene expression alterations.

Methods

We preformed RNA-Seq for one pair of GCA and matched non-tumor tissues. Differentially expressed genes (DEGs) and fusion genes were acquired. PCR and gel analysis in additional 14 pairs of samples were performed to validate the chimeric transcripts.

Results

1590 up-regulated and 709 down-regulated genes were detected. Functional analysis revealed that these DEGs were significantly overrepresented in gene ontology items of cell cycle, tumor invasion and proliferation. Moreover, we firstly discovered 3 fusion genes in GCA, including BMX-ARHGAP, LRP5- LITAF and CBX3-C15orf57. The chimeric transcript BMX-ARHGAP was validated and recurrently occurred in 4/15 independent tumor tissues.

Conclusions

Our results may provide new understanding of GCA and biomarkers for further therapeutic studies.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​13000_​2014_​218
Appendix
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Literature
1.
Shen L, Shan Y-S, Hu H-M, Price TJ, Sirohi B, Yeh K-H, Yang Y-H, Sano T, Yang H-K, Zhang X, Park SR, Fujii M, Kang Y-K, Chen L-T: Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol. 2013, 14: e535-e547. 10.1016/S1470-2045(13)70436-4.PubMedCrossRef
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.PubMedCrossRef
3.
Nagini S: Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012, 4: 156-169. 10.4251/wjgo.v4.i7.156.PubMedPubMedCentralCrossRef
4.
Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM: Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005, 241: 27-39.PubMedPubMedCentral
5.
Brown LM, Devesa SS: Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am. 2002, 11: 235-256. 10.1016/S1055-3207(02)00002-9.PubMedCrossRef
6.
Orengo MA, Casella C, Fontana V, Filiberti R, Conio M, Rosso S, Tumino R, Crosignani P, De Lisi V, Falcini F, Vercelli M, Group AW: Trends in incidence rates of oesophagus and gastric cancer in Italy by subsite and histology, 1986–1997. Eur J Gastroenterol Hepatol. 2006, 18: 739-746. 10.1097/01.meg.0000223905.78116.38.PubMedCrossRef
7.
Fock KM: Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther. 2014, 40: 250-260. 10.1111/apt.12814.PubMedCrossRef
8.
Piazuelo MB, Correa P: Gastric cancer: overview. Colombia Medica. 2013, 44: 192-201.PubMed
9.
10.
Langmead B, Trapnell C, Pop M, Salzberg SL: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009, 10: R25-10.1186/gb-2009-10-3-r25.PubMedPubMedCentralCrossRef
11.
Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL: TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013, 14: R36-10.1186/gb-2013-14-4-r36.PubMedPubMedCentralCrossRef
12.
Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP: Integrative genomics viewer. Nat Biotechnol. 2011, 29: 24-26. 10.1038/nbt.1754.PubMedPubMedCentralCrossRef
13.
Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L: Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012, 7: 562-578. 10.1038/nprot.2012.016.PubMedPubMedCentralCrossRef
14.
da Huang W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009, 4: 44-57. 10.1038/nprot.2008.211.PubMedCrossRef
15.
Katz Y, Wang ET, Airoldi EM, Burge CB: Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat Methods. 2010, 7: 1009-1015. 10.1038/nmeth.1528.PubMedPubMedCentralCrossRef
16.
McPherson A, Hormozdiari F, Zayed A, Giuliany R, Ha G, Sun MG, Griffith M, Heravi Moussavi A, Senz J, Melnyk N, Pacheco M, Marra MA, Hirst M, Nielsen TO, Sahinalp SC, Huntsman D, Shah SP: deFuse: an algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput Biol. 2011, 7: e1001138-10.1371/journal.pcbi.1001138.PubMedPubMedCentralCrossRef
17.
18.
Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD: MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature. 2011, 471: 377-381. 10.1038/nature09754.PubMedPubMedCentralCrossRef
19.
Kim HP, Cho GA, Han SW, Shin JY, Jeong EG, Song SH, Lee WC, Lee KH, Bang D, Seo JS, Kim JI, Kim TY: Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis.Oncogene 2013, doi:10.1038/onc.2013.490.,
20.
Tao J, Deng NT, Ramnarayanan K, Huang B, Oh HK, Leong SH, Lim SS, Tan IB, Ooi CH, Wu J, Lee M, Zhang S, Rha SY, Chung HC, Smoot DT, Ashktorab H, Kon OL, Cacheux V, Yap C, Palanisamy N, Tan P: CD44-SLC1A2 gene fusions in gastric cancer. Sci Transl Med. 2011, 3: 77ra30-10.1126/scitranslmed.3001423.PubMed
21.
Li H, Guo L, Li J, Liu N, Liu J: Alternative splicing of RHAMM gene in chinese gastric cancers and its in vitro regulation. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2000, 17: 343-347.PubMed
22.
Pal S, Gupta R, Davuluri RV: Alternative transcription and alternative splicing in cancer. Pharmacol Ther. 2012, 136: 283-294. 10.1016/j.pharmthera.2012.08.005.PubMedCrossRef
23.
Banky B, Raso-Barnett L, Barbai T, Timar J, Becsagh P, Raso E: Characteristics of CD44 alternative splice pattern in the course of human colorectal adenocarcinoma progression. Mol Cancer. 2012, 11: 83-10.1186/1476-4598-11-83.PubMedPubMedCentralCrossRef
24.
Heim S, Mitelman F: Molecular screening for new fusion genes in cancer. Nat Genet. 2008, 40: 685-686. 10.1038/ng0608-685.PubMedCrossRef
25.
Schrider DR, Navarro FC, Galante PA, Parmigiani RB, Camargo AA, Hahn MW, de Souza SJ: Gene copy-number polymorphism caused by retrotransposition in humans. PLoS Genet. 2013, 9: e1003242-10.1371/journal.pgen.1003242.PubMedPubMedCentralCrossRef
26.
Chen K, Navin NE, Wang Y, Schmidt HK, Wallis JW, Niu B, Fan X, Zhao H, McLellan MD, Hoadley KA, Mardis ER, Ley TJ, Perou CM, Wilson RK, Ding L: BreakTrans: uncovering the genomic architecture of gene fusions. Genome Biol. 2013, 14: R87-10.1186/gb-2013-14-8-r87.PubMedPubMedCentralCrossRef
27.
Guo S, Sun F, Guo Z, Li W, Alfano A, Chen H, Magyar CE, Huang J, Chai TC, Qiu S, Qiu Y: Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy. PLoS ONE. 2011, 6: e17778-10.1371/journal.pone.0017778.PubMedPubMedCentralCrossRef
28.
Cenni B, Gutmann S, Gottar-Guillier M: BMX and its role in inflammation, cardiovascular disease, and cancer. Int Rev Immunol. 2012, 31: 166-173. 10.3109/08830185.2012.663838.PubMedCrossRef
29.
Gentile A, D’Alessandro L, Lazzari L, Martinoglio B, Bertotti A, Mira A, Lanzetti L, Comoglio PM, Medico E: Met-driven invasive growth involves transcriptional regulation of Arhgap12. Oncogene. 2008, 27: 5590-5598. 10.1038/onc.2008.173.PubMedCrossRef
Metadata
Title
Identification of a novel gene fusion (BMX-ARHGAP) in gastric cardia adenocarcinoma
Authors
Xiaofeng Xu
Lifang Xu
Feng Gao
Jianjiang Wang
Jinsong Ye
Mingxian Zhou
Yunling Zhu
Lan Tao
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2014
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-014-0218-4

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