Journal of Diagnostics Concepts & Practice ›› 2019, Vol. 18 ›› Issue (06): 685-671.doi: 10.16150/j.1671-2870.2019.06.017
• Review article • Previous Articles Next Articles
Received:2018-10-19
Online:2019-12-25
Published:2019-12-25
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| 技术 | 可检测的变异形式 | 定性或定量 | 优势 | 不足 | 灵敏度或 分辨率 | 检测时机 | 报告时 间（d） |
|---|---|---|---|---|---|---|---|
| 二代测序 | 可同时检测已知和未知 突变 | 定性或半 定量 | 通量高,可同时检测 多个位点、多种突 变类型,节省样本 | 数据分析及报告解 读较为复杂 | 1%~5% | 初诊及治疗后 | 10~14 |
| 一代测序 | 多为已知突变,可检测点 突变、小片段插入缺失 以及拷贝数变异 | 定性 | 方便、快速、经济, 结果易于分析 | 灵敏度不高, 通量低 | 10%~20% | 初诊 | 3~5 |
| PCR | 检测已知突变,包括单核 苷酸变异、小片段插入 或缺失、基因融合 | 定性或相 对定量 | 方便、快速、经济 | 通量低,1个反应检 测1个变异,最 多不超过5个 变异 | 0.1% | 初诊、动态监测、 检测微小残 留病 | 3~5 |
| 数字PCR | 检测已知突变,主要为 单核苷酸变异、小片段 插入或缺失或基因融合 | 绝对定量 | 高灵敏度,绝对定量 | 需要特殊设备, 价格高 | 0.01%~0.10% | 动态监测,检测微 小残留病 | 3~5 |
| 荧光原位杂交 | 检测已知突变,可检测大 片段插入、缺失及基因 融合、重排、扩增 | 定性 | 分子诊断金标准 | 通量低 | 20~100 kb | 初诊 | 5~7 |
| 核型分析 | 可同时检测已知和未知 染色体数目和结构变异 | 定性 | 经济,可以一次分析 全基因组 | 分辨率低, 灵敏度低 | 5~10 Mb | 初诊 | 7~14 |
| 染色体微阵列 | 可同时检测已知和未知 突变,多用于检测拷贝 数变化 | 定性 | 可以一次分析 全基因组 | 数据分析及报告 解读较为复杂 | 50~100 kb | 初诊 | 10~14 |
| 突变基因 | 与MDS疾病相关的典型的 突变类型和位置 | 发生频率 | 临床意义 | 生物学功能 |
|---|---|---|---|---|
| TET2 | 无义突变、移码突变、剪切位点 突变、错义突变（氨基酸1134~ 1444或1842~1921） | 20%~25% | 与正常核型相关,常见于CMML（40%~60%） | 表观遗传学修饰 |
| DNMT3A | 无义突变、移码突变、剪切位点 突变、错义突变（氨基酸R882） | 12%~18% | 在AML中发生频率更高 | 表观遗传学修饰 |
| ASXL1 | 无义突变、移码突变 | 15%~25% | MDS的独立预后因子,与不良预后相关 | 表观遗传学修饰 |
| EZH2 | 无义突变、移码突变 | 5%~10% | MDS的独立预后因子,与不良预后相关 | 表观遗传学修饰 |
| SF3B1 | 错义突变包括E622、Y623、 R625、N626、H662、T663、K666, K700E、I704、G740、G742、D781 | 20%~30% | 与RS增多特异性相关,特别是MDS-RS中更 常见（80%）;可作为辅助诊断指标; 是独立预后因子,与预后良好相关 | RNA剪切因子 |
| SRSF2 | 错义突变P95 | 10%~15% | 在CMML中更常见（40%）,与不良预后相关 | RNA剪切因子 |
| U2AF1 | 错义突变S34、Q157 | 8%~12% | 与不良预后相关 | RNA剪切因子 |
| ZRSR2 | 无义突变、移码突变 | 5%~10% | 与不良预后相关 | RNA剪切因子 |
| TP53 | 无义突变、移码突变、剪切位点 突变、任意位置的错义突变, 除了P47S和P72R | 8%~12% | 独立预后因子,与不良预后相关。多发生于复杂 核型（50%）和5q缺失（15%~20%）;可能预测 复发及对来那度胺不敏感 | DNA损伤和修复 |
| STAG2 | 无义突变、移码突变、剪切位点 突变 | 5%~10% | 与不良预后相关 | 姐妹染色体结合和分离 |
| NRAS | 错义突变G12、G13、Q61 | 5%~10% | 与不良预后相关,特别是被预测为低风险的 MDS患者;多见于CMML和JMML (~15%) | 信号转导 |
| CBL | 错义突变366~420 | <5% | 多见于CMML (10%~20%) 及JMML （15%） | 调节蛋白质降解及多个信 号通路,包括RAS通路 |
| JAK2 | 错义突变V617F | <5% | 多见于伴RS及血小板增多的MDS或MPN, 与 SF3B1突变一起发生 | 信号转导 |
| NF1 | 无义突变、移码突变、剪切位点 突变 | <5% | 多见于CMML（5%~10%）及JMML （15%） | 信号转导 |
| RUNX1 | 无义突变、移码突变 | 10%~15% | 独立预后因子,与不良预后相关;在少见病例中 与遗传性肿瘤相关 | 转录因子 |
| ETV6 | 无义突变、移码突变 | <5% | 独立预后因子,与不良预后相关;在少见病例中 与遗传性肿瘤相关 | 转录因子 |
| IDH1 | 错义突变R132 | <5% | 多见于AML | 表观遗传学修饰 |
| IDH2 | 错义突变R140Q、R172 | <5% | 多见于AML, 与不良预后相关 | 表观遗传学修饰 |
| SETBP1 | 错义突变E858、T864、I865, D868、S869、G870 | <5% | 与疾病进展相关;多见于CMML（5%~10%） 和JMML（7%） | 表观遗传学修饰 |
| PHF6 | 无义突变、移码突变、剪切位点 突变 | <5% | 多见于原始细胞增多,与生存没有相关性 | 表观遗传学修饰 |
| BCOR | 无义突变、移码突变、剪切位点 突变、错义突变N1425 | <5% | 与不良预后相关, 多见于CMML（5%~10%） | 转录调节因子,表观遗传 学修饰 |
| STAT3 | 错义突变（氨基酸584~674） | <5% | 发生于大颗粒淋巴细胞白血病相关的MDS, 与免疫性骨髓衰竭相关 | 信号转导,与JAK通路 相关 |
| PPM1D | 无义突变、移码突变 | ~5% | 与MDS治疗相关,与TP53相关的不良预后 无关 | DNA损伤和修复 |
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