Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (5): 971-974. doi: 10.19723/j.issn.1671-167X.2020.05.030

Previous Articles     Next Articles

Concordant point mutation of ETS-related gene (ERG) in tumor tissues from a synchronous multiple primary lung cancer: A case report

Yi BAO1,2,∆(),Juan-fen MO2   

  1. 1. Department of Oncology, The Second Hospital of Jiaxing, Jiaxing 314000, Zhejiang, China
    2. Key Laboratory, The Second Hospital of Jiaxing, Jiaxing 314000, Zhejiang, China
  • Received:2018-10-16 Online:2020-10-18 Published:2020-10-15
  • Contact: Yi BAO E-mail:ybao2011@gmail.com
  • Supported by:
    Science and Technology Bureau of Jiaxing(2016AY23054);Health Bureau of Zhejiang Province(2016KYB292)

RICH HTML

   

PDF (PC)

Abstract:

The rearrangement of the gene encoding the transcription factor ETS-related gene (ERG) is thought to play a key role in the development of prostate cancer. However, the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma (NSCLC). Here, we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs. The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography (CT) scan. After conducting lobectomies at the both lungs, the tumor nodules were all removed, and the histological analysis suggested adenocarcinoma at the both tumor lesions. The patient was diagnosed with synchronous multiple primary lung cancer (SMPLC) based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines. An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC. Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score. The read depth was ≥ 1 000× and the depth of coverage was 95%. The data revealed a discordant epidermal growth factor receptor (EGFR) from the separate lungs; additionally, a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions. This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC. This study suggests that the same environment may contribute certain gene(s) mutations in the same sites in the early stages of polyclonal tumor origins; meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.

Key words: Lung neoplasms, Neoplasms, multiple primary, ETS-related gene, Mutation, High-throughput nucleotide sequencing

CLC Number: 

  • R734.2

Figure 1

The images of chest computed tomography (CT) before surgeries A, the arrow showed a size of 2.0 cm×2.0 cm lesion with irregular high density shadow at the upper lobe of right lung; B, the arrow showed a size of 1.4 cm×3.3 cm with ground glass nodule in the bottom lobe of left lung. "

Table 1

Comparison of somatic cell gene mutation with mutaton frequency ≥5% between the two separate tumor lesions"

Items Tumor nodule Gene Chromosome location Gene mutation Density Mutation frequency
Discordant (≥5%) Left side EGFR 7p11.2 exon21,c.2573T>G,p.L858R 1 844 15%(290/1 884)
ACVR1B 12q13.13 exon2,c.106T>A,p.C36S 554 9%(48/554)
GRIN2A 16p13.2 exon11,c.2326G>A,p.D776N 647 9% (56/647)
ATR 3q23 exon47,c.7912C>T,p.L2638F 483 7% (32/483)
EGFR 7p11.2 exon19,c.2240T>C,p.L747S 2 906 7% (207/2 906)
CBFR 16q22.1 exon5,c.481C>T,p.R161W 951 5% (48/951)
NF1 17q11.2 exon33,c.4462C>T,p.R1488C 775 5% (35/775)
NOTCH2 1p12 exon34,c.7153A>C,p.T2385P 914 5% (44/914)
Right side ARID2 12q12 exon5,c.539G>A,p.C180Y 588 6%(34/588)
ARID2 12q12 exon15,c.1960C>G,p.P654A 1 058 5% (48/1 058)
Concordant(≥5%) Left side ERG 21q22.2 exon9,c.929A>C,p.H310P 637 9% (60/637)
Right side ERG 21q22.2 exon9,c.929A>C,p.H310P 929 8% (74/929)

Figure 2

The mutation of ERG was analyzed from the TCGA non-small-cell lung carcinoma samples by using the cBioportal data analysis platform"

Figure 3

The correlation of ERG mutation and overall survival was analyzed from the TCGA non-small-cell lung carcinoma samples by using the cBioportal data analysis platform"

[1] Kumar-Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer[J]. Nat Rev Cancer, 2008,8(7):497-511.
doi: 10.1038/nrc2402 pmid: 18563191
[2] Brenner JC, Ateeq B, Li Y, et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer[J]. Cancer Cell, 2011,19(5):664-678.
doi: 10.1016/j.ccr.2011.04.010
[3] Wang X, Qiao Y, Asangani IA, et al. Development of peptidomimetic inhibitors of the ERG gene gusion product in prostate cancer[J]. Cancer Cell, 2017,31(4):532-548.
doi: 10.1016/j.ccell.2017.02.017 pmid: 28344039
[4] Martini N, Melamed MR. Multiple primary lung cancers[J]. J Thorac Cardiovasc Surg, 1975,70(4):606-612.
pmid: 170482
[5] Kozower BD, Larner JM, Detterbeck FC. Special treatment issues in non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines[J]. Chest, 2013,143(5 Suppl):e369S-e399S.
doi: 10.1378/chest.12-2362 pmid: 23649447
[6] Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin[J]. Cancer, 1953,6(5):963-968.
doi: 10.1002/1097-0142(195309)6:5<963::aid-cncr2820060515>3.0.co;2-q pmid: 13094644
[7] Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma[J]. Nature, 2014,511(7511):543-550.
doi: 10.1038/nature13385
[8] Jamal-Hanjani M, Wilson GA, McGranahan N, et al. Tracking the evolution of non-small-cell lung cancer[J]. N Engl J Med, 2017,376(22):2109-2121.
doi: 10.1056/NEJMoa1616288 pmid: 28445112
[9] Adamo P, Ladomery MR. The oncogene ERG: A key factor in prostate cancer[J]. Oncogene, 2016,35(4):403-414.
doi: 10.1038/onc.2015.109 pmid: 25915839
[10] Ida K, Kobayashi S, Taki T, et al. EWS-FLI-1 and EWS-ERG chimeric mRNAs in Ewing’s sarcoma and primitive neuroectodermal tumor[J]. Int J Cancer, 1995,63(4):500-504.
doi: 10.1002/ijc.2910630407 pmid: 7591257
[11] Nagai N, Ohguchi H, Nakaki R, et al. Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition[J]. PLoS Genet, 2018,14(11):e1007826.
doi: 10.1371/journal.pgen.1007826 pmid: 30500808
[1] Jiafu JI, Jingtao WEI, Ke JI, Zhaode BU. Bottlenecks and breakthroughs in gastric cancer diagnosis and treatment: Towards a new era of precision and intelligent integration [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 231-238.
[2] Jiale GAO, Zhongtao ZHANG. Current status and future perspectives of precision treatment for locally advanced rectal cancer [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 247-250.
[3] Bixian LUO, Hongming LIU, Weixun XIE, Weihua GONG. Novel clinical insights and frontier issues in alpha- fetoprotein-producing gastric cancer [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 257-265.
[4] Youdong LIU, Yajun LYU, Jie CHEN, Mingde ZANG, Hongda PAN, Xiaowen LIU, Jun LU, Fenglin LIU. Clinical efficacy and safety of totally laparoscopic subtotal gastrectomy with cardia-gastric fundus preservation in middle-upper gastric cancer [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 301-306.
[5] Jialin LI, Liqiao CHEN, Jiatian TANG, Yan WU, Anqiang WANG. Conversion therapy for hepatoid adenocarcinoma of the stomach: A case report [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 399-404.
[6] Bin LI, Han LIANG. Robotic gastrectomy: Research progress and practical challenges [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 416-422.
[7] Yanhua LIU, Min LU, Xuyang ZHAO, Kuan'gen ZHANG, Rui WU, Fang MEI, Zhihao DAI, Jiangfeng YOU, Fei PEI. Effect of dephosphorylation of tumor metastasis suppressor gene LASS2 on vacuolar ATPase activity and invasiveness of prostate cancer [J]. Journal of Peking University (Health Sciences), 2025, 57(6): 1113-1123.
[8] Qi DONG, Jing HE, Yuan JIA, Haihong YAO, Xia ZHANG. VEXAS syndrome mimicking relapsing polychondritis: A case report [J]. Journal of Peking University (Health Sciences), 2025, 57(6): 1180-1183.
[9] Xiaoyong YANG, Fan ZHANG, Lulin MA, Cheng LIU. Clinical characteristics and influencing factors of extraglandular invasion of prostatic ductal adenocarcinoma [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 956-960.
[10] Jiaxin NING, Haoran WANG, Shuhang LUO, Jibo JING, Jianye WANG, Huimin HOU, Ming LIU. Multi-omics analysis of the relationship between oxidative stress-related gene and prostate cancer [J]. Journal of Peking University (Health Sciences), 2025, 57(4): 633-643.
[11] Zeyuan WANG, Shuanbao YU, Haoke ZHENG, Jin TAO, Yafeng FAN, Xuepei ZHANG. A preoperative prediction model for pelvic lymph node metastasis in prostate cancer: Integrating clinical characteristics and multiparametric MRI [J]. Journal of Peking University (Health Sciences), 2025, 57(4): 684-691.
[12] Shuai LIU, Zhuo LIU, Yunhe GUAN, Guoliang WANG, Xiaojun TIAN, Hongxian ZHANG, Lei LIU, Lulin MA, Shudong ZHANG. Robot-assisted laparoscopic inferior vena cava segmental resection for renal tumor with tumor thrombus invading the vascular wall [J]. Journal of Peking University (Health Sciences), 2025, 57(4): 796-802.
[13] Dan HAN, Yangjin CIREN, Qiuhong LI, Jun LI. Changes of intestinal microflora in patients with colorectal benign and malignant tumors in high altitude area and comparison with the normal population in low altitude area [J]. Journal of Peking University (Health Sciences), 2025, 57(3): 578-583.
[14] Yanlei WANG, Min DUAN, Jianzhong XIAO, Wenhui ZHAO. Abnormal elevation of growth hormone in patients with pituitary adenoma combined with cirrhosis: A case report [J]. Journal of Peking University (Health Sciences), 2025, 57(2): 400-402.
[15] Guangyan YU, Xin PENG, Min GAO, Peng YE, Na GE, Mengqi JIA, Bingyu LI, Zunan TANG, Leihao HU, Wenbo ZHANG. Research progress in diagnosis and treatment of salivary gland tumors [J]. Journal of Peking University (Health Sciences), 2025, 57(1): 1-6.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd