Dutrillaux B
UA 620 CNRS, Institut Curie, Section de biologie, Paris, France.
Bull Cancer. 1988;75(6):509-16.
A brief description of the results obtained by cytogenetic analyses of cancer cells from colorectal adenocarcinomas is reported. Two distinct patterns of chromosomal anomalies are observed. The major one, called "monosomic type", because many chromosomes losses exist, is characterised by the losses or deletions of the following chromosomes 18, 17 (short arm = p), 1p, 4, 14, 5 (long arm = q) and 21. It frequently evolves towards polyploidy, by duplication of all remaining chromosomes. The minor one, called "trisomic type", is characterised by the gain of several chromosomes: 7, 12, X, 5 and 8. The chromosomal anomalies observed seem to have no topological relationships with oncogenes, and other interpretations for their occurrence were investigated. The numerous and frequent deletions of some chromosomes, like 17p and 18, may indicate the involvement of recessive genes, like in the anti-oncogene system. In addition, it is observed that most deletions involve genes for "de novo" pathways whereas gains involve genes for salvage pathways of the synthesis of nucleotides. A correlated cytogenetic and enzymologic study was thus developed, and the first results show that the chromosomal pattern may well indicate the metabolic deviations. Monosomic type tumors have, on the average, a relatively low "de novo" and a high salvage pathways, and trisomic type tumors a high "de novo" and salvage pathways. Since chemotherapy is principally orientated against "de novo" pathways of the synthesis of nucleotides, these results may help to understand the difficulties of chemotherapy in colorectal cancers and perhaps to adapt it better.
本文报道了结直肠癌癌细胞的细胞遗传学分析结果。观察到两种不同的染色体异常模式。主要的一种称为“单体型”,因为存在许多染色体缺失,其特征是以下染色体的缺失:18、17(短臂 = p)、1p、4、14、5(长臂 = q)和21。它经常通过所有剩余染色体的复制演变为多倍体。次要的一种称为“三体型”,其特征是几条染色体的增加:7、12、X、5和8。观察到的染色体异常似乎与癌基因没有拓扑关系,并对其发生的其他解释进行了研究。一些染色体,如17p和18的大量频繁缺失,可能表明隐性基因的参与,就像在抗癌基因系统中一样。此外,观察到大多数缺失涉及“从头合成”途径的基因,而增加涉及核苷酸合成补救途径的基因。因此开展了一项相关的细胞遗传学和酶学研究,初步结果表明染色体模式很可能表明代谢偏差。单体型肿瘤平均具有相对较低的“从头合成”途径和较高的补救途径,而三体型肿瘤具有较高的“从头合成”途径和补救途径。由于化疗主要针对核苷酸合成的“从头合成”途径,这些结果可能有助于理解结直肠癌化疗的困难,并可能更好地调整化疗方案。