Malins Donald C, Gilman Naomi K, Green Virginia M, Wheeler Thomas M, Barker Edward A, Vinson Mark A, Sayeeduddin Mohammad, Hellström Karl Erik, Anderson Katie M
Biochemical Oncology Program, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA.
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11428-31. doi: 10.1073/pnas.0404572101. Epub 2004 Jul 27.
Fourier transform-infrared statistical models have the proven ability to identify subtle structural changes in DNA at various stages of tumor development. Using these models, we show evidence for a metastatic cancer DNA phenotype in histologically normal prostate tissues surrounding metastasizing tumors. Strikingly, the DNA base and backbone structures of the metastatic phenotype are indistinguishable from those of the metastasizing prostate tumors but distinctly different from the structure recently reported for the primary cancer DNA phenotype. These findings suggest that the DNA structure linked to the development of metastasis is preordained in progenitor cells relatively early in multistep tumorigenesis. The substantial structural differences found between the primary and metastatic cancer DNA phenotypes suggest that each evolves through a separate pathway. The metastatic phenotype is potentially an early predictor of metastatic disease. Interventions that inhibit its formation would be expected to also inhibit the development of metastatic tumors.
傅里叶变换红外统计模型已被证明有能力识别肿瘤发展各阶段DNA中的细微结构变化。利用这些模型,我们发现有证据表明,在发生转移的肿瘤周围组织学上正常的前列腺组织中存在转移性癌DNA表型。令人惊讶的是,转移表型的DNA碱基和骨架结构与发生转移的前列腺肿瘤无法区分,但与最近报道的原发性癌DNA表型的结构明显不同。这些发现表明,与转移发展相关的DNA结构在多步骤肿瘤发生过程中相对较早阶段的祖细胞中就已预先确定。原发性和转移性癌DNA表型之间存在的显著结构差异表明,它们各自通过不同的途径演变。转移表型可能是转移性疾病的早期预测指标。预计抑制其形成的干预措施也会抑制转移性肿瘤的发展。