您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (11): 82-88.doi: 10.6040/j.issn.1671-7554.0.2023.0510

• • 上一篇    

SMARCA2缺失的未分化肠癌4例并文献复习

李喆1,张振坤2,张淑坤3   

  1. 1.潍坊医学院, 山东 潍坊 261053;2.寿光市人民医院肿瘤科, 山东 潍坊 262700;3.威海市立医院病理科, 山东 威海 264200
  • 发布日期:2023-12-12
  • 通讯作者: 张淑坤. E-mail:zhangshukun0475@126.com

SMARCA2-deficient undifferentiated bowel cancer: a report of 4 cases and literature review

LI Zhe1, ZHANG Zhenkun2, ZHANG Shukun3   

  1. 1. Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Oncology, Shouguang Peoples Hospital, Weifang 262700, Shandong, China;
    3. Department of Pathology, Weihai Municipal Hospital, Weihai 264200, Shandong, China
  • Published:2023-12-12

摘要: 目的 探究SMARCA2缺失的未分化肠癌这一组特殊类型肿瘤的临床病理学特征。 方法 收集2016年1月至2020年12月在威海市立医院诊断为未分化肠癌并且SMARCA2阴性的病例资料,由高年资医师重新检查苏木精-伊红(HE)染色切片,观察其组织学形态,再次确定未分化形态。使用自动免疫组化染色机对患者的甲醛固定石蜡包埋的组织块提取的代表性切片进行免疫组织化学染色。 结果 共入组4例病例,均于1年内死亡,HE切片下表现为高度恶性的形态。 结论 SMARCA2缺失是一种预后差的指标,其可能是肿瘤去分化过程的一环。对SMARCA2在这类肿瘤的确切作用和作用机制尚未明确。SMARCA2作为一种潜在的治疗靶点,也可能是一种评价预后的标志物,具有一定研究价值。

关键词: SWI/SNF复合体, SMARCA2缺失, 未分化, 肠癌, 临床病理学特征

Abstract: Objective To explore the clinicopathological features of SMARCA2-deficient undifferentiated bowel cancer. Methods Clinical data of patients with undifferentiated bowel cancer and negative SMARCA2 expression diagnosed in Weihai Municipal Hospital during Jan. 2016 and Dec. 2020 were collected. The sections of HE staining were re-examined, the histological morphology was re-observed, and the undifferentiated morphology was re-determined by senior pathologists. The representative sections extracted from paraffin-embedded formalin-fixed tissue blocks were stained with automatic immunohistochemical staining machine. Results All four patients died within 1 year. HE staining showed highly malignant morphology. Conclusion SMARCA2 depletion is an indicator of poor prognosis and may be involved in tumor dedifferentiati

Key words: SWI/SNF complex, SMARCA2 depletion, Undifferentiation, Bowel cancer, Clinicopathological features

中图分类号: 

  • R365
[1] Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system[J]. Histopathology, 2020, 76(2): 182-188.
[2] Peterson CL, Dingwall A, Scott MP. Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement[J]. Proc Natl Acad Sci U S A, 1994, 91(8): 2905-2908.
[3] Centore RC, Sandoval GJ, Soares LMM, et al. Mammalian SWI/SNF chromatin remodeling complexes: emerging mechanisms and therapeutic strategies[J]. Trends Genet, 2020, 36(12): 936-950.
[4] Masliah-Planchon J, Bièche I, Guinebretière JM, et al. SWI/SNF chromatin remodeling and human malignancies[J]. Annu Rev Pathol, 2015, 10: 145-171.
[5] Raab JR, Runge JS, Spear CC, et al. Co-regulation of transcription by BRG1 and BRM, two mutually exclusive SWI/SNF ATPase subunits[J]. Epigenetics Chromatin, 2017, 10(1): 62.
[6] Marquez-Vilendrer SB, Rai SK, Gramling SJ, et al. Loss of the SWI/SNF ATPase subunits BRM and BRG1 drives lung cancer development[J]. Oncoscience, 2016, 3(11/12): 322-336.
[7] Bultman S, Gebuhr T, Yee D, et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes[J]. Mol Cell, 2000, 6(6): 1287-1295.
[8] Reyes JC, Barra J, Muchardt C, et al. Altered control of cellular proliferation in the absence of mammalian Brahma(SNF2alpha)[J]. EMBO J, 1998, 17(23): 6979-6991.
[9] Coisy-Quivy M, Disson O, Roure V, et al. Role for Brm in cell growth control[J]. Cancer Res, 2006, 66(10): 5069-5076.
[10] Villatoro TM, Ma CQ, Pai RK. Switch/sucrose nonfermenting nucleosome complex-deficient colorectal carcinomas have distinct clinicopathologic features[J]. Hum Pathol, 2020, 99: 53-61.
[11] Cohet N, Stewart KM, Mudhasani R, et al. SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells[J]. J Cell Physiol, 2010, 223(3): 667-678.
[12] Kobayashi H, Kawahara N, Ogawa K, et al. Conceptual frameworks of synthetic lethality in clear cell carcinoma of the ovary[J]. Biomed Rep, 2018, 9(2): 112-118.
[13] Yang M, Sun Y, Ma L, et al. Complex alternative splicing of the smarca2 gene suggests the importance of smarca2-B variants[J]. J Cancer, 2011, 2: 386-400.
[14] Huang SC, Ng KF, Chang IY, et al. The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes[J]. PLoS One, 2021, 16(1): e0245356. doi:10.1371/journal.pone.0245356.
[15] Jancewicz I, Siedlecki JA, Sarnowski TJ, et al. BRM: the core ATPase subunit of SWI/SNF chromatin-remodelling complex-a tumour suppressor or tumour-promoting factor?[J]. Epigenetics Chromatin, 2019, 12(1): 68.
[16] SUN S, LI Q, ZHANG Z, et al. SMARCA2 deficiency in NSCLC: a clinicopathologic and immunohistochemical analysis of a large series from a single institution [J]. Environ Health Prev Med, 2022, 27: 3. doi: 10.1265/ehpm.21-00254.
[17] Glaros S, Cirrincione GM, Muchardt C, et al. The reversible epigenetic silencing of BRM: implications for clinical targeted therapy[J]. Oncogene, 2007, 26(49): 7058-7066.
[18] Kahali B, Gramling SJ, Marquez SB, et al. Identifying targets for the restoration and reactivation of BRM[J]. Oncogene, 2014, 33(5): 653-664.
[19] Bourachot B, Yaniv M, Muchardt C. Growth inhibition by the mammalian SWI-SNF subunit Brm is regulated by acetylation[J]. EMBO J, 2003, 22(24): 6505-6515.
[20] Kahali B, Yu JL, Marquez SB, et al. The silencing of the SWI/SNF subunit and anticancer gene BRM in rhabdoid tumors[J]. Oncotarget, 2014, 5(10): 3316-3332.
[21] Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation[J]. Nat Rev Drug Discov, 2014, 13(5): 337-356.
[22] Shorstova T, Marques M, Su J, et al. SWI/SNF-compromised cancers are susceptible to bromodomain inhibitors[J]. Cancer Res, 2019, 79(10): 2761-2774.
[23] McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations[J]. Nature, 2012, 492(7427): 108-112.
[24] Knutson SK, Warholic NM, Wigle TJ, et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2[J]. Proc Natl Acad Sci U S A, 2013, 110(19): 7922-7927.
[25] Kawano S, Grassian AR, Tsuda M, et al. Preclinical evidence of anti-tumor activity induced by EZH2 inhibition in human models of synovial sarcoma[J]. PLoS One, 2016, 11(7): e0158888. doi:10.1371/journal.pone.0158888.
[26] Song XJ, Zhang LD, Gao TT, et al. Selective inhibition of EZH2 by ZLD10A blocks H3K27 methylation and kills mutant lymphoma cells proliferation[J]. Biomedecine Pharmacother, 2016, 81: 288-294.
[27] Januario T, Ye XF, Bainer R, et al. PRC2-mediated repression of SMARCA2 predicts EZH2 inhibitor activity in SWI/SNF mutant tumors[J]. Proc Natl Acad Sci U S A, 2017, 114(46): 12249-12254.
[28] Chan-Penebre E, Armstrong K, Drew A, et al. Selective killing of SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type cells by inhibition of EZH2: in vitro and in vivo preclinical models[J]. Mol Cancer Ther, 2017, 16(5): 850-860.
[29] Wang NY, Qin Y, Du FR, et al. Prevalence of SWI/SNF genomic alterations in cancer and association with the response to immune checkpoint inhibitors: a systematic review and meta-analysis[J]. Gene, 2022, 834: 146638. doi:10.1016/j.gene.2022.146638.
[30] Jancewicz I, Szarkowska J, Konopinski R, et al. PD-L1 overexpression, SWI/SNF complex deregulation, and profound transcriptomic changes characterize cancer-dependent exhaustion of persistently activated CD4+ T cells[J]. Cancers, 2021, 13(16): 4148.
[1] 董雅琪,王新慧,赵颖慧,王传新. 血清外泌体LINC02163作为结直肠癌远处转移标志物的临床价值[J]. 山东大学学报 (医学版), 2023, 61(9): 19-28.
[2] 赵迪,吕高荣,李国鹏,张云雪,王伟民,董晓玲,厉萍. 14条目和6条目弗莱堡正念调查量表在胃肠癌患者中的心理测量学评价[J]. 山东大学学报 (医学版), 2023, 61(6): 87-91.
[3] 孙富云,王维鹏,张会会,耿艳,安小霞,李双双,张彬彬. 结直肠癌术后患者人格特质与抑郁、焦虑症状的关联性[J]. 山东大学学报 (医学版), 2021, 59(7): 91-96.
[4] 杜甜甜,李娟,赵颖慧,段伟丽,王景,王允山,杜鲁涛,王传新. 长链非编码RNA LINC02474在结直肠癌中的表达特征及对细胞增殖的影响[J]. 山东大学学报 (医学版), 2021, 59(10): 59-69.
[5] 甄秋来,吕欣然,叶辉,丁绪超,柴小雪,胡辛,周明,曹莉莉. 基于TCGA数据库预测结肠癌预后基因及其临床应用价值[J]. 山东大学学报 (医学版), 2021, 59(1): 64-71.
[6] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38-46.
[7] 王天霄,李静,李海林. 网络问卷结直肠早癌筛查效果的初步评估[J]. 山东大学学报 (医学版), 2020, 58(4): 90-94.
[8] 洪甲庚,聂洋洋,苏国强. 丙泊酚对结肠癌细胞增殖、迁移及Wnt1和β-catenin表达的影响[J]. 山东大学学报 (医学版), 2020, 58(11): 53-58.
[9] 王海锋,王刚,赵健,刘江,周嘉晖,江志伟. 加速康复外科在直肠癌腹会阴联合切除术中的应用[J]. 山东大学学报 (医学版), 2019, 57(9): 33-37.
[10] 周嘉晖,王刚,刘江,赵健,王海锋,江志伟. 加速康复外科指导下的多模式镇痛对开腹结肠癌患者术后恢复的影响[J]. 山东大学学报 (医学版), 2019, 57(9): 38-42.
[11] 吴成威,孙博实,周军德,蒋天明,迟强. 术前口服多糖溶液对结直肠癌患者术后胰岛素抵抗的关联性研究[J]. 山东大学学报 (医学版), 2019, 57(9): 48-53.
[12] 李乐平,崔怀平,商亮. 加速康复外科在胃肠外科手术中的应用[J]. 山东大学学报 (医学版), 2019, 57(9): 5-11.
[13] 郭艳,张哲莹,王云溪,魏小娟. 人源性长寿保障基因2在结直肠癌组织中的表达及其临床意义[J]. 山东大学学报 (医学版), 2019, 57(7): 67-71.
[14] 万秀霞,孙秀萍,佟晶洁. 大黄酚对结肠癌的抗肿瘤作用[J]. 山东大学学报 (医学版), 2019, 57(5): 74-79.
[15] 耿旭,张璐,李明,卢志明. 多种肿瘤自身抗体对结直肠癌诊断的应用价值[J]. 山东大学学报 (医学版), 2019, 57(4): 65-71.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!