Giaretti W
Laboratory of Biophysics, National Institute for Cancer Research, Genoa, Italy.
Lab Invest. 1994 Dec;71(6):904-10.
Extensive chromosome and DNA content heterogeneity within and between human solid tumors has been observed using both classical karyotype and DNA cytometry. Experimental evidence suggests, at least in some tumor types, that DNA stemline heterogeneity in tumor progression is according to a three-compartment model with diploidy shifting to tetraploidy and then to hypotetraploidy.
The human colorectal adenoma-carcinoma sequence appears as one of the most potentially informative systems for the study of DNA stemline heterogeneity in human tumors since adenomas, adenomas with early cancer, and adenocarcinomas in nontreated patients represent clear morphologically distinct stages of tumor progression. The quantitative measurement of DNA content in the G0.1 phase of the cell cycle was performed by high resolution flow cytometry in a large number of cases using multiple fresh or frozen samples.
The distribution of the degree of DNA aneuploidy values, also known as DNA index, (DI not equal to 1) among 467 human precancer and cancer colorectal lesions was clearly nonrandom and showed modes at DI = 0.9, 1.2, 1.5, 1.8, and 2.2 with a clear valley at DI = 1.3. Whereas DNA aneuploid subclones within early lesions were up to about 80% near-diploid (DI < or = 1.3), DNA subclones within advanced cancer were in the vast majority with DI = 1.5-1.8 and, in a small fraction, with DI > 2. In addition, in adenomas with early cancer, which represent a link in colorectal tumor progression, early and late DNA stemlines often coexisted.
The natural history of the colorectal adenoma-carcinoma sequence appears to be characterized by near-diploid subclones as early events and by late-stage hypotetraploidy. A new model is proposed that predicts the origin of the near-diploid subclones by "loss of symmetry" in cell division and their evolution (in particular hypodiploid) to the late-stage hypotetraploidy by tetraploidization. This model agrees with recent data associating molecular biology events, cytogenetic data, and DNA stemline heterogeneity in colorectal and other tumor systems.
使用经典核型分析和DNA细胞计量术已观察到人类实体瘤内部以及不同实体瘤之间存在广泛的染色体和DNA含量异质性。实验证据表明，至少在某些肿瘤类型中，肿瘤进展过程中的DNA干系异质性符合一个三室模型，即从二倍体转变为四倍体，然后再转变为亚四倍体。
人类结直肠腺瘤-癌序列似乎是研究人类肿瘤中DNA干系异质性最具潜在信息价值的系统之一，因为腺瘤、伴有早期癌的腺瘤以及未经治疗患者的腺癌代表了肿瘤进展过程中形态学上明显不同的阶段。通过高分辨率流式细胞术，使用多个新鲜或冷冻样本，对大量病例的细胞周期G0.1期的DNA含量进行了定量测量。
在467例人类结直肠癌前病变和癌性病变中，DNA非整倍体值（也称为DNA指数，DI不等于1）的分布明显非随机，在DI = 0.9、1.2、1.5、1.8和2.2处出现峰态，在DI = 1.3处有明显低谷。早期病变中的DNA非整倍体亚克隆中近二倍体（DI≤1.3）的比例高达约80%，而晚期癌中的DNA亚克隆绝大多数DI = 1.5 - 1.8，一小部分DI>2。此外，在伴有早期癌的腺瘤中，这代表了结直肠肿瘤进展中的一个环节，早期和晚期DNA干系常共存。
结直肠腺瘤-癌序列的自然史似乎以早期的近二倍体亚克隆和晚期的亚四倍体为特征。提出了一个新模型，该模型通过细胞分裂中的“对称性丧失”预测近二倍体亚克隆的起源，以及它们通过四倍体化演变为晚期亚四倍体（特别是亚二倍体）的过程。该模型与最近将分子生物学事件、细胞遗传学数据以及结直肠和其他肿瘤系统中的DNA干系异质性相关联的数据一致。
