甲状腺乳头状癌组织常染色体和性染色体STR基因座变异分析

doi:10.3969/j.issn.1004-616x.2019.05.007

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (5): 373-378,384.doi: 10.3969/j.issn.1004-616x.2019.05.007

甲状腺乳头状癌组织常染色体和性染色体STR基因座变异分析

刘奇^1,2, 张海霞¹, 董婷婷³, 党珍¹, 侯秀迪², 赵帅², 韩亚文², 王业全^1,2, 崔文^1,2

1. 济宁医学院法医学与医学检验学院, 山东济宁 272067;
2. 济宁医学院司法鉴定中心, 山东济宁 272013;
3. 青岛大学医学部, 山东青岛 266071

收稿日期:2019-04-17 修回日期:2019-09-11 出版日期:2019-09-30 发布日期:2019-10-09
通讯作者: 王业全,E-mail:wangyequan1103@163.com;崔文,E-mail:cuiwenmd@163.com E-mail:wangyequan1103@163.com;cuiwenmd@163.com
作者简介:刘奇,E-mail:qiliu0451@163.com。
基金资助:
济宁医学院教师科研扶持基金（JYFC2018FY004，JY2017FY001）

Mutational analysis of STR loci genomic changes in human papillary thyroid cancers

LIU Qi^1,2, ZHANG Haixia¹, DONG Tingting³, Dang Zhen¹, HOU Xiudi², ZHAO Shuai², HAN Yawen², WANG Yequan^1,2, CUI Wen^1,2

1. Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining 272067;
2. Forensic Science Center of Jining Medical University, Jining 272013;
3. Department of Medicine, Qiingdao University, Qiingdao 266071, Shandong, China

Received:2019-04-17 Revised:2019-09-11 Online:2019-09-30 Published:2019-10-09

摘要/Abstract

摘要： 目的：探讨甲状腺乳头状癌组织中短串联重复序列（STR）基因座变异规律以及显微切割技术在肿瘤组织鉴定中的应用，为甲状腺乳头状癌组织的个体识别及亲缘关系鉴定提供依据。方法：收集43例人甲状腺乳头状癌和癌旁正常组织经激光显微切割获取肿瘤细胞和间质细胞，采用Chelex-100法提取DNA，分别采用Goldeneye^® DNA 22NC、Goldeneye^® DNA 27YB和Goldeneye^® DNA 17X试剂盒进行常染色体和性染色体STR基因座PCR扩增，ABI 3500遗传分析仪检测进行STR分型。结果：甲状腺乳头状癌组织肿瘤间质细胞与对应癌旁组织的STR分型一致。43例癌组织的肿瘤细胞有9例STR基因座发生了变异，在常染色体和X染色体联合检测的37个STR基因座共检出11次变异（常染色体变异7次，X染色体变异4次），其中等位基因增加3次，部分杂合性丢失6次，出现新等位基因2次，并且同一甲状腺乳头状癌肿瘤细胞可同时发生多种变异。Y染色体STR基因座没有检出变异。结合实验结果与患者临床资料分析，STR基因座的变异与甲状腺乳头状癌患者的临床分期、性别无明显相关关系，与患者的年龄正相关，差异具有统计学意义（P < 0.05）。结论：甲状腺恶性肿瘤组织常染色体和X染色体STR基因座存在变异，而且变异更可能发生在年龄大的甲状腺乳头状癌组织中，在司法鉴定中进行STR分型时应谨慎判型。显微切割技术可准确分离间质细胞，是解决此类恶性肿瘤组织检材涉及的案件进行身源鉴定的有效手段。

关键词: 显微切割, 短串联重复序列, 基因变异, 人甲状腺乳头状癌

Abstract: OBJECTIVE:To investigate genomic alterations in STR loci on autosomal and sex chromosomes among human papillary thyroid cancers. METHODS:Tumor and stromal cells were separated from papillary thyroid cancer tissues from 43 unrelated patients using laser capture microdissection. DNA of tumor cells,stromal cells and adjacent normal tissues were extracted using Chelex-100,amplified using Goldeneye^® DNA 22NC,Goldeneye^® DNA 27YB and Goldeneye^® DNA 17X PCR amplification kit and analyzed using ABI 3500 Genetic Analyzer. RESULTS:The genotypes of stromal cells from different cancer tissues were consistent with that from corresponding adjacent normal tissues. Genomic alterations were detected in 11 out of 43 tumor cell specimens. Eleven alterations were detected on 37 STR loci within autosomal and X chromosomes,including additional alleles:3 times,partial loss of heterozygosity:6 times,and new alleles:2 times. Moreover,the alternations might have occur simultaneously at more than one loci in the same tumor cells. There were no genomic alterations detected on STR loci of the Y chromosome. With respect to clinical data,there was no significant association between STR variations and staging of the cancers,nor patient's gender. However,there were significant differences between age of the patients and STR loci alterations (P < 0.05). CONCLUSION:There were genomic alterations in the STR loci among autosomal and sex chromosomes in human papillary thyroid cancer cells. In addition,these alterations occurred more often in older patients. Stromal cells could be separated accurately from tumor tissues by microdissection which would provide more opportunity for investigations.

Key words: microdissection, short tandem repeats, genetic alterations, papillary thyroid cancer

中图分类号:

R736.1

刘奇, 张海霞, 董婷婷, 党珍, 侯秀迪, 赵帅, 韩亚文, 王业全, 崔文. 甲状腺乳头状癌组织常染色体和性染色体STR基因座变异分析[J]. 癌变·畸变·突变, 2019, 31(5): 373-378,384.

LIU Qi, ZHANG Haixia, DONG Tingting, Dang Zhen, HOU Xiudi, ZHAO Shuai, HAN Yawen, WANG Yequan, CUI Wen. Mutational analysis of STR loci genomic changes in human papillary thyroid cancers[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(5): 373-378,384.

参考文献

[1] 方建新, 李成涛, 肖立. 13个STR位点在人消化系统肿瘤组织中的变异分析[J]. 法医学杂志, 2007, 23(4):280-282.
[2] MUCH M, BUZA N, HUI P. Tissue identity testing of cancer by short tandem repeat polymorphism:pitfalls of interpretation in the presence of microsatellite instability[J]. Hum Pathol, 2014, 45(3):549-555.
[3] 刘争, 赵华, 罗志永, 等. 乳腺癌与癌前病变微卫星DNA杂合性缺失研究[J]. 中国实验诊断学, 2011, 15(4):592-595.
[4] PELTOM-KI P, LOTHE R A, AALTONEN L A, et al. Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome[J]. Cancer Res, 1993, 53(24):5853-5855.
[5] 孙丽娟, 李淑瑾, 付光平, 等. 妇科肿瘤和乳腺癌组织常染色体和X染色体STR的突变分析[J]. 中国法医学杂志, 2017, 32(4):350-353, 358.
[6] GILL P, BRENNER C H, BUCKLETON J S, et al. DNA commission of the international society of forensic genetics:recommendations on the interpretation of mixtures[J]. Forensic Sci Int, 2006, 160(2/3):90-101.
[7] 李成涛, 赵书民, 张素华, 等. 肿瘤组织中部分杂合性丢失判定标准的适用性评估[J]. 法医学杂志, 2009, 25(6):417-420.
[8] 杨燕青, 张雯, 张宝峰, 等. 激光显微切割分离细胞的微量RNA质量鉴定体系的建立[J]. 遗传, 2008, 30(11):1521-1526.
[9] LIU Y, LI L, LI C T, et al. Allelic alterations of STRs in archival paraffin embedded tissue as DNA source for paternity testing[J]. Forensic Sci Int:Genet Suppl Ser, 2009, 2(1):12-13.
[10] 刘彬, 吴泽妮, 刘潇阳, 等. 人乳头瘤病毒与子宫颈腺癌病因关系研究[J]. 中华肿瘤杂志, 2016, 38(4):277-282.
[11] 马若翔, 李永国, 朱英, 等. 肺癌组织中STR基因座变异规律的研究[J]. 中国癌症杂志, 2017, 27(5):353-358.
[12] 熊剑丁. 甲状腺乳头状癌中基因突变的研究进展[J]. 吉林医学, 2018, 39(9):1767-1769.
[13] 丛文铭. 肿瘤抑制基因变异的分子病理学研究进展[J]. 中华病理学杂志, 2001, 30(1):58-60.
[14] 王小春, 王明荣. 染色体不稳定性的机制及其与肿瘤的关系[J]. 肿瘤防治研究, 2010, 37(6):719-722.
[15] PRESS M O, CARLSON K D, QUEITSCH C. The overdue promise of short tandem repeat variation for heritability[J]. Trends Genet, 2014, 30(11):504-512.

甲状腺乳头状癌组织常染色体和性染色体STR基因座变异分析

Mutational analysis of STR loci genomic changes in human papillary thyroid cancers

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