Monoclonal origins of malignant mixed tumors (carcinosarcomas) - Evidence for a divergent histogenesis
Monoclonal origins of malignant mixed tumors (carcinosarcomas) - Evidence for a divergent histogenesis
复制标题
DOI：
10.1097/00000478-199603000-00003
复制
发表时间：
1996-03-01
影响因子：
5.6
通讯作者：
Barsky, SH
中科院分区：
文献类型：
--
作者：
Thompson, L;Chang, B;Barsky, SH
恶性混合瘤（癌瘤）是罕见肿瘤的例子，其发生已被观察到在日益多样化的网站，但其发病机制仍然是一个完整的谜。两个对立的假说，已提出来解释这些肿瘤的组织发生，包括收敛假说，提出了从两个或两个以上的干细胞（多克隆假说）的起源，和发散假说，提出了从一个全能干细胞分化成不同的上皮和间充质方向（单克隆假说）的起源。为了检验这些假设，使用了一种新的策略来确定来自通过酶消化新鲜或福尔马林固定的石蜡包埋组织和细胞分选获得的少至100个肿瘤细胞的克隆性，该策略显示聚合酶链反应（PCR）扩增位于人次黄嘌呤磷酸核糖转移酶基因的第一内含子内的511-bp区域，一个含有无活性X染色体专性甲基化HpaII/MspI位点和5%女性单碱基等位基因多态性的位点。基于异硫氰酸荧光素（FITC）-抗细胞角蛋白门控的癌细胞和基于FITC-抗波形蛋白或FITC-抗结蛋白门控的肉瘤细胞在FACSTAR上分选至均一，然后在PCR扩增之前进行基因组DNA提取和Hpa II消化，随后在变性梯度凝胶电泳上分析产物。在从四个不同器官获得的六种不同恶性混合瘤中，癌细胞和肉瘤细胞产生的单个同双链体的共迁移表明在所有情况下都具有克隆同一性和单克隆性。这些单克隆性的发现被另外两种克隆性测定方法独立地证实。癌细胞瘤的单克隆起源的研究结果支持单一全能干细胞分化假说。
Malignant mixed tumors (carcinosarcomas) are examples of unusual neoplasms whose occurrences have been observed in increasingly diverse sites but whose pathogenesis remains a complete mystery. Two antithetical hypotheses that have been advanced to explain the histogenesis of these tumors include the convergence hypothesis, which proposes an origin from two or more stem cells (multiclonal hypothesis), and the divergence hypothesis, which proposes an origin from a single totipotential stem cell that differentiates into separate epithelial and mesenchymal directions (monoclonal hypothesis). To test these hypotheses, a novel strategy for the determination of clonality from as few as 100 tumor cells obtained by enzymatic digestion of either fresh or formalin-fixed, paraffin-embedded tissues and cell sorting was used that exhibited the polymerase chain reaction (PCR) in amplifying a 511-bp region located within the first intron of the human hypoxanthine phosphoribosyl transferase gene, a site that contains inactive X chromosomal obligately methylated HpaII/MspI sites and single-base allelic polymorphisms in 5% females. Carcinoma cells gated on the basis of fluorescein isothiocyanate (FITC)-anti-cytokeratin and sarcoma cells gated on the basis of FITC-antivimentin or FITC-anti-desmin were sorted to homogeneity on FACSTAR and then subjected to genomic DNA extraction and Hpa II digestion before PCR amplification and subsequent analysis of the product on denaturing gradient gel electrophoresis. The comigrations of the single homoduplexes generated from both the carcinoma cells and sarcoma cells in six different malignant mixed tumors obtained from four different organs indicated clonal identity and monoclonality in all cases. These findings of monoclonality were confirmed independently by two other methods of clonality determination. The findings of a monoclonal origin of carcinosarcomas support the single totipotential stem-cell-divergence hypothesis.