Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma

Oxford University Press (OUP) - Tập 5 - Trang 1-14 - 2016
Caixia Cheng1,2,3, Heyang Cui1,2, Ling Zhang1,2, Zhiwu Jia1,2, Bin Song1,2,4, Fang Wang1,2, Yaoping Li1,5, Jing Liu1,6, Pengzhou Kong1,2, Ruyi Shi1,2, Yanghui Bi1,2, Bin Yang1,2,5, Juan Wang1,2, Zhenxiang Zhao1,2, Yanyan Zhang1,6, Xiaoling Hu1,2, Jie Yang1,2, Chanting He1,2, Zhiping Zhao1,2, Jinfen Wang7, Yanfeng Xi7, Enwei Xu7, Guodong Li7, Shiping Guo5, Yunqing Chen5, Xiaofeng Yang8, Xing Chen9, Jianfang Liang3, Jiansheng Guo6, Xiaolong Cheng1,2, Chuangui Wang10, Qimin Zhan11, Yongping Cui1,2
1Translational Medicine Research Center, Shanxi Medical University, Taiyuan, China
2Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China
3Department of Pathology, First Hospital of Shanxi Medical University, Taiyuan, China
4Department of Oncology, First Hospital of Shanxi Medical University, Taiyuan, China
5Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, China
6Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, China
7Department of Pathology, Shanxi Cancer Hospital, Taiyuan, China
8Department of Urology Surgery, First Hospital of Shanxi Medical University, Taiyuan, China
9Department of Endoscopy, Shanxi Provincial People’s Hospital, Taiyuan, China
10Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
11Cancer Institute and Cancer Hospital, State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Tóm tắt

Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples. Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC. Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility.

Tài liệu tham khảo

Dubecz A, Gall I, Solymosi N, Schweigert M, Peters JH, Feith M, et al. Temporal trends in long-term survival and cure rates in esophageal cancer: a SEER database analysis. J ThoracOncol. 2012;7:443–7. Tran GD, Sun XD, Abnet CC, Fan JH, Dawsey SM, Dong ZW, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer. 2005;113:456–63. Gao Y, Hu N, Han X, Giffen C, Ding T, Goldstein A, et al. Family history of cancer and risk for esophageal and gastric cancer in Shanxi. China BMC Cancer. 2009;9:269. Engel LS, Chow WH, Vaughan TL, Gammon MD, Risch HA, Stanford JL, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst. 2003;95:1404–13. Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381:400–12. Okuno T, Tamura T, Yamamori M, Chayahara N, Yamada T, Miki I, et al. Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese. Am J ClinOncol. 2007;30:252–7. Kuwahara A, Yamamori M, Nishiguchi K, Okuno T, Chayahara N, Miki I, et al. Effect of dose-escalation of 5-fluorouracil on circadian variability of its pharmacokinetics in Japanese patients with Stage III/Iva esophageal squamous cell carcinoma. Int J Med Sci. 2010;7:48–54. Kuwahara A, Yamamori M, Nishiguchi K, Okuno T, Chayahara N, Miki I, et al. Replacement of cisplatin with nedaplatin in a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. Int J Med Sci. 2009;6:305–11. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associatedgenes. Nature. 2013;499:214–8. Zhang H, Xu L, Xiao D, Xie J, Zeng H, Cai W, et al. Fascin is a potential biomarker for early‐stage oesophageal squamous cell carcinoma. J ClinPathol. 2006;59:958–64. Yang YL, Chu JY, Luo ML, Wu YP, Zhang Y, Feng YB, et al. Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Gene Chromosome Canc. 2008;47:127–36. Jarmuz-Szymczak M, Pelinska K, Kostrzewska-Poczekaj M, Bembnista E, Giefing M, Brauze D, et al. Heterogeneity of 11q13 region rearrangements in laryngeal squamous cell carcinoma analyzed by microarray platforms and fluorescence in situ hybridization. Mol Biol Rep. 2013;40:4161–71. Hu N, Wang C, Ng D, Clifford R, Yang HH, Tang ZZ, et al. Genomic characterization of esophageal squamous cell carcinoma from a high-risk population in China. Cancer Res. 2009;69:5908–17. Song Y, Li L, Ou Y, Gao Z, Li E, Li X, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 2014;509:91–5. Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X, et al. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet. 2014;46:467–73. Gao YB, Chen ZL, Li JG, Hu XD, Shi XJ, Sun ZM, et al. Genetic landscape of esophageal squamous cell carcinoma. Nat Genet. 2014;46:1097–102. Zhang L, Zhou Y, Cheng CX, Cui HY, Cheng L, Kong PZ, et al. Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma. Am J Hum Genet. 2015;96(4):597–611. Cui Y, Borysova MK, Johnson JO, Guadagno TM. Oncogenic B-RafV600E induces spindle abnormalities, supernumerary centrosomes, and aneuploidy in human melanocytic cells. Cancer Res. 2010;70:675–84. Dulak AM, Stojanov P, Peng S, Lawrence MS, Fox C, Stewart C, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478–86. Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D, et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci U S A. 2007;104:20007–12. Miyawaki Y, Kawachi H, Ooi A, Eishi Y, Kawano T, Inazawa J, et al. Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma. Cancer Sci. 2012;103:1558–66. Krzystek-Korpacka M, Matusiewicz M, Diakowska D, Grabowski K, Blachut K, Banas T. Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Cancer Lett. 2007;249:171–7. Yokobori T, Mimori K, Iwatsuki M, Ishii H, Tanaka F, Sato T, et al. Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma. Int J Oncol. 2012;41:253–9. Yan S, Zhou C, Lou X, Xiao Z, Zhu H, Wang Q, et al. PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. Cancer Res. 2009;69:3283–90. Forghanifard MM, Moaven O, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, et al. Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis. Ann Surg Oncol. 2012;19:743–9. McDonald WH, Pavlova Y, Yates JR, Boddy MN. Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5–Smc6 complex. J Biol Chem. 2003;278:45460–7. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333:1154–7. Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318:1108–13. Hammerman PS, Lawrence MS, Voet D, Jing R, Cibulskis K, Sivachenko A, et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519–25. Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, et al. Gauging NOTCH1 activation in cancer using immunohistochemistry. PLoS One. 2013;8, e67306. Kanatsu-Shinohara M, Onoyama I, Nakayama KI, Shinohara T. Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal. Proc Natl Acad Sci U S A. 2014;111:8826–31. Le Gallo M, O’Hara AJ, Rudd ML, Urick ME, Hansen NF, O’Neil NJ, et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat Genet. 2012;44:1310–5. Aydin IT, Melamed RD, Adams SJ, Castillo-Martin M, Demir A, Bryk D, et al. FBXW7 mutations in melanoma and a new therapeutic paradigm. J Natl Cancer Inst. 2014;106:dju107. Agrawal N, Jiao Y, Bettegowda C, Hutfless SM, Wang Y, David S, et al. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov. 2012;2:899–905. Chen X, Zhang T, Shi J, Xu P, Gu Z, Sandham A, et al. Notch1 signaling regulates the proliferation and self-renewal of human dental follicle cells by modulating the g1/s phase transition and telomerase activity. PLoS One. 2013;8, e69967. Ranganathan P, Weaver KL, Capobianco AJ. Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer. 2011;11:338–51. Hales EC, Taub JW, Matherly LH. New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis: targeted therapy of γ-secretase inhibitor resistant T-cell acute lymphoblastic leukemia. Cell Signal. 2014;26:149–61. Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, et al. Gauging NOTCH1 activation in cancer using immunohistochemistry. PLoS One. 2013;8, e67306. Paganin M, Ferrando A. Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia. Blood Rev. 2011;25:83–90. Klinakis A, Lobry C, Abdel-Wahab O, Oh P, Haeno H, Buonamici S, et al. A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature. 2011;473:230–3. Wang NJ, Sanborn Z, Arnett KL, Bayston LJ, Liao W, Proby CM, et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci U S A. 2011;108:17761–6. Ogawa R, Ishiguro H, Kimura M, Funahashi H, Wakasugi T, Ando T, et al. NOTCH1 expression predicts patient prognosis in esophageal squamous cell cancer. Eur Surg Res. 2013;51:101–7. Agilent SureSelect in Solution,http://www.halogenomics.com/sureselect/how-it-works Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60. Cao Y, He M, Gao Z, Peng Y, Li Y, Li L, et al. Activating hotspot L205R mutation in PRKACA and adrenal Cushing’s syndrome. Science. 2014;344:913–7. Xu H, DiCarlo J, Satya RV, Peng Q, Wang Y. Comparison of somatic mutation calling methods in amplicon and whole exome sequence data. BMC Genomics. 2014;15:244–53. Stead LF, Sutton KM, Taylor GR, Quirke P, Rabbitts P. Accurately identifying low-allelic fraction variants in single samples with next-generation sequencing: applications in tumor subclone resolution. HumMutat. 2013;34:1432–8. Wang Q, Jia P, Li F, Chen H, Ji H, Hucks D, et al. Detecting somatic point mutations in cancer genome sequencing data: a comparison of mutation callers. Genome Med. 2013;5:91–8. Koboldt DC, Chen K, Wylie T, Larson DE, McLellan MD, Mardis ER, et al. VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics. 2009;25:2283–5. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164. Short Oligonucleotide Analysis Package, http://soap.genomics.org.cn/ McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303. Chiang DY, Getz G, Jaffe DB, O’Kelly MJ, Zhao X, Carter SL, et al. High-resolution mapping of copy-number alterations with massively parallel sequencing. Nat Methods. 2009;6:99–103. Parmigiani G, Boca S, Lin J, Kinzler KW, Velculescu V, Vogelstein B. Design and analysis issues in genome-wide somatic mutation studies of cancer. Genomics. 2009;93:17–21. MutSigCV, http://www.broadinstitute.org/cancer/cga/mutsig KEGG database, http://www.genome.jp/kegg Zhang L, Shi R, He C, Cheng C, Song B, Cui H, et al. Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells. Cancer Lett. 2013;337:125–32. Liu J, Cheng X, Zhang Y, Li S, Cui H, Zhang L, et al. Phosphorylation of Mps1 by BRAFV600E Prevents Mps1 degradation and contributes to chromosome instability in Melanoma. Oncogene. 2013;32:713–23. Lal S, La Du J, Tanguay RL, Greenwood JA. Calpain 2 is required for the invasion of glioblastoma cells in the zebrafish brain microenvironment. J Neurosci Res. 2012;90:769–81. Vagnarelli P, Hudson DF, Ribeiro SA, Trinkle-Mulcahy L, Spence JM, Lai F, et al. Condensin and Repo-Man-PP1 co-operate in the regulation of chromosome architecture during mitosis. Nat Cell Biol. 2006;8:1133–42. Cheng C, Cui H, Zhang L, Jia Z, Song B, Wang F, et al. Supporting data for “Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma”. GigaScience Database. 2015. htpp://doi.org/10.5524/100181
Thông tin
Thông tin xuất bản

Oxford University Press (OUP)

Tập 5

1-14

Thông tin tác giả