Nielsen Torsten O, West Rob B, Linn Sabine C, Alter Orly, Knowling Margaret A, O'Connell John X, Zhu Shirley, Fero Mike, Sherlock Gavin, Pollack Jonathan R, Brown Patrick O, Botstein David, van de Rijn Matt
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Lancet. 2002 Apr 13;359(9314):1301-7. doi: 10.1016/S0140-6736(02)08270-3.
Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers.
We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition.
Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types.
These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.
软组织肿瘤起源于间充质细胞，如成纤维细胞、肌肉细胞或脂肪细胞，但对于许多此类肿瘤，其组织发生仍存在争议。我们旨在启动对这些罕见肿瘤的分子特征分析，并进行全基因组搜索以寻找新的诊断标志物。
我们使用点阵cDNA微阵列分析了41例软组织肿瘤的基因表达模式。在去除因使用不同微阵列批次而引入的误差后，利用5520个定义明确的基因的表达模式，通过层次聚类和奇异值分解将肿瘤分为不同的组。
滑膜肉瘤、胃肠道间质瘤、神经肿瘤以及平滑肌肉瘤的一个子集，显示出截然不同的基因表达模式。其他肿瘤类别——恶性纤维组织细胞瘤、脂肪肉瘤和其余的平滑肌肉瘤——具有共同的分子特征，这是组织学特征或免疫组织化学无法预测的。在区分不同肉瘤的基因集中，注意到已知基因如胃肠道间质瘤中的KIT的强表达。然而，许多未表征的基因也有助于区分肿瘤类型。
这些结果提示了一种软组织肿瘤分类的新方法，该方法可能优于基于组织学发现的方法。大量未表征的基因促成了肿瘤之间的区分，其中一些可能是有用的诊断标志物，具有预后意义，或可能成为治疗靶点。
