Medical Diagnosis
Vol.06 No.04(2016), Article ID:19353,5 pages
10.12677/MD.2016.64016

The Analysis of Chromosome Amplification in Different Tumors

Bo Liu1*, Zhi Wang1, Yixiong Liu2#, Linni Fan2#

1Seventh Company, Second Battalion, First Brigade, The Fourth Military Medical University, Xi’an Shaanxi

2School of Basic Medical Sciences, The Fourth Military Medical University, Xi’an Shaanxi

Received: Dec. 2nd, 2016; accepted: Dec. 20th, 2016; published: Dec. 23rd, 2016

Copyright © 2016 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

ABSTRACT

As more and more scientific research scholars focus on the tumor gene, the relationship between chromosome amplification and malignant tumors has been revealed and validated. By discussing the chromosome variation in different malignant tumors, this paper reveals the rule of common chromosome mutations, concisely provides the new detection methods and clinical therapeutic targets and helps the application of new technologies and drugs.

Keywords:Chromosome, Tumors, Amplification

不同肿瘤染色体的扩增分析

刘博1*,王智1,刘一雄2#,范林妮2#

1第四军医大学,一旅二营七连,陕西 西安

2第四军医大学基础部,陕西 西安

收稿日期:2016年12月2日;录用日期:2016年12月20日;发布日期:2016年12月23日

摘 要

随着越来越多的科研学者将肿瘤关注的重点投入到基因方面,染色体扩增与恶性肿瘤的关系不断被揭示和验证。本文通过探讨不同恶性肿瘤中染色体变异情况,揭示了常见染色体突变的规律,同时简洁地为临床上新的检测方法和治疗靶点提供了依据。有助于新技术和新药物的应用开展。

关键词 :染色体,肿瘤,扩增

1. 引言

近年来我国有越来越多的学者将精力投入到肿瘤研究上,在流行病、病因、基础、诊断与治疗等方面的研究均取得了可喜的成绩。特别是在基因水平上进行了深入的研究。大量文献表明肿瘤的发生与癌基因激活和抑癌基因失活有密切关系。而染色体拷贝数变异在肿瘤的发生发展过程中起到了一个重要事件。染色体扩增可导致癌基因表达上调,而染色体缺失可导致抑癌基因表达缺失。DNA异倍体是染色体异常的表型,也是细胞癌变的特征指标,与恶性肿瘤的异常增殖相关 [1] ,一般来说在染色体水平鉴定循环肿瘤细胞(CTC)更为客观及准确。不同实体瘤存在不同的染色体异常情况,具体分析说明如下:

2. 乳腺癌

乳腺癌患者中8号及17号染色体异常表达情况较为普遍,阳性率较高 [2] [4] ,并且同位于其上的c-myc/HER2/TOP2A等基因及乳腺癌Ki67/ER/病理分型等临床指标密切相关 [3] ,针对8/17号染色体倍体情况的分析,可以给予乳腺癌临床诊治判断提供有效的依据。

例如8号染色体的异常表达是浸润性导管癌的不良预后相关 [4] 。而在17号染色体的倍体分析中,与病理分级/ER表达/Nottingham指数等多种不良预后预测因子显著相关 [3] [5] [6] 。在治疗方面,多中心临床试验证实在CEP17多体情况下CEF方案组患者获益明显强于CMF组 [7] 。对于TOP2A基因调控的蒽环类药物治疗方面,CEP17多体情况下同蒽环类药敏性可获得提升 [3] [8] 。在靶向治疗预测方面,在IHC方法HER 3+情况下,CEP17非多体的患者对于单纯靶向方案不敏。

3. 肺癌

肺癌患者中8号染色体异常表达情况较为普遍,呈现较高比例的非整倍体性 [9] ;生存方面分析显示:CEP8非整倍体比例同生存期呈负相关(显著性差异),即CEP8扩增比例大,5年生存期短 [10] ;同时,位于8号染色体上的c-myc基因扩增表达提示预后差,同时两种(CMYC扩增/P53缺失)同转移相关。而CEP8的扩增同位于其上的c-myc及P53的表达呈正相关,故CEP8的扩增与CEP17的缺失具有指导预后及转移的作用 [11] 。8号染色体扩增的CTC在不同分期的非小细胞肺癌患者中均有相对较高比例的表达,同时在以正常人及肺部良性疾病患者的对照组中,呈现较高的特异性,与其他肺癌相关瘤标对比,基于8号染色体扩增的CTC检测的灵敏性优于瘤标检测;在对接受化疗的晚期非小细胞肺癌患者治疗前、治疗后的CTC检测数目变化考察中,结果显示:CTC评价疗效结果显示出与影像学的高度一致性;同时以CTC基线值及变化值为考量因素,则对患者的PFS有更精准的预测 [12] 。

4. 肝癌

肝癌患者中1号及8号染色体呈现高比例的异常表达 [13] ;其中1号染色体尤其是位于1号染色体上的三体情况较为普遍且在正常肝组织与良性病灶中无异常,显示出较高的特异性 [14] 。

同时,基于FISH技术考察1/8号染色体在于高/中/低分化程度的肝细胞癌中的分布情况。结果显示随着病理去分化程度的上升,1/8号染色体倍体数目呈现明显的上升趋势(p ≤ 0.0002),提示染色体不稳定性(chromosomal instability, CIN)程度随病理分化程度的下降而提升 [15] 。

5. 结直肠癌

结直肠癌患者中呈现不同比例的7号、8号染色体扩增情况 [16] 。7号染色体多体现象显示出与MET和MACC1高表达相关 [17] 。而在肝转移患者中往往呈现7号染色体高频异常,8号染色体出现缺失、增益、扩增等现象 [16] 。

6. 卵巢癌

卵巢癌患者中8号染色体扩增表达在晚期浆液性卵巢癌患者中呈现高表达,早期浆液性中则表达较少 [18] 。8号染色体上的c-myc有无扩增与年龄及预后相关,其中c-myc扩增与卵巢子宫内膜异位的恶性转化相关 [19] 。8号染色体扩增型CTC在浆液性及非浆液性卵巢癌患者中均有不同比例的表达,同时CTC数目与CA125水平存在相关性,且较之CA125,灵敏性更高 [20] 。

7. 胰腺癌

胰腺癌患者中8号染色体存在不同比例的扩增及缺失现象 [21] 。针对胰腺导管癌的研究显示:8号染色体上的c-myc基因的表达在胰腺癌侵袭过程中呈现下降的现象,结果指出c-myc扩增可能与胰腺导管癌早期发生发展有关,而与局部肿瘤的侵袭性相关性不大 [22] 。以8号染色体扩增为鉴别标识的CTC的检测研究中显示:不同分期的胰腺癌患者均有较高的CTC检出率;对接受手术的胰腺癌患者的随访显示:术后CTC阳性患者有更差的预后生存 [23] 。

8. 胃癌

胃癌患者中的17号染色体多体同肿瘤位置/远端转移/姑息手术效果/术后并发症存在显著相关性。其中的HER2扩增与低度浸润/高分化呈现极高相关性 [24] 。在进展期胃癌患者中,无论是治疗前还是治疗后8号染色体扩增的CTC均有较高的检出率。对接受化疗的AGC患者分别于治疗前、治疗后分别进行CTC检测结果显示:PR的患者治疗前8号染色体三体所占比例最低。治疗后:PR和SD的患者8号染色体四体及多体比例都明显下降,而PD患者中却上升。提示8号染色体三体存在原始性耐药,而四体与多体与用药敏感性及获得性耐药相关 [25] 。

随着越来越多的学者将肿瘤研究的关注点转移到基因水平,人们对肿瘤的检测和治疗也上升了一个新的高度。目前已有很多基因ALK, HER2, EGFR等靶向药物投入临床,在提高肿瘤病人的生存期和改善预后等方面取得十分积极的成果。另一方面,现代医学诊疗手段特别是病理分子技术的日渐成熟已经为肿瘤疾病的诊治提供了新的依据和方法。诸如FISH技术,以及基于FISH原理的CTCS和肿瘤相关的巨噬样细胞(CAMLS)均普遍运用于临床检测。虽然目前分子诊断还不能取代传统的组织活检,但是新技术的运用大大提高了临床病理报告的准确性和可靠性。每一项新技术的出现和普及都要经过一个较长的过程,但是笔者相信随着对于染色体的研究更加深入成熟,在此基础上衍生出来的技术和手段终将会成为人类攻克肿瘤的一大利器。

文章引用

刘博,王智,刘一雄,范林妮. 不同肿瘤染色体的扩增分析
The Analysis of Chromosome Amplification in Different Tumors[J]. 医学诊断, 2016, 06(04): 89-93. http://dx.doi.org/10.12677/MD.2016.64016

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  26. NOTES

    *第一作者。

    #通讯作者。

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