Kölble K, Ullrich O M, Pidde H, Barthel B, Diermann J, Rudolph B, Dietel M, Schlag P M, Scherneck S
Tumorgenetik, Max-Delbrück-Centrum für Molekulare Medizin, Klinik für Chirurgie und Chirurgische Onkologie, Robert-Rössle-Klinik, Berlin, Germany.
Lab Invest. 1999 Sep;79(9):1145-50.
Cell-free DNA in the blood of cancer patients has been shown to harbor microsatellite alterations frequently matching those of the primary tumors. The aim of this study was to assess the prevalence of allelic loss and instability of serum DNA microsatellites in colorectal cancers. DNA extracted from preoperative sera and microdissected tumors of 27 patients with colorectal adenocarcinoma were allelotyped for nine markers on chromosome arms 1p, 5q, 8p, 12p, 15q, 17p, 17q, and 18q. In all tumors, expression of MLH1 and MSH2 was explored immunohistochemically. Microsatellite alterations comprising loss of heterozygosity (LOH) or microsatellite instability (MSI) were present in 26 of 27 (96%) tumors and in 16 of 27 (59%) serum samples. Using stringent criteria, serum MSI was significantly (p < 0.02) more detectable than serum LOH. Of the three patients with high-grade MSI (more than two unstable loci) present in tumor and serum DNA, two had MSH2-negative tumors on immunohistochemical testing. No significant association of tumor stage or clinical outcome with serum microsatellite alterations of LOH or MSI type could be demonstrated. Although the DNA-shedding phenotype of tumors remains to be elucidated, its detection by serum DNA microsatellite analysis seems to be useful for the diagnosis and monitoring of neoplasms, including colorectal cancers with and without MSI.
癌症患者血液中的游离DNA已被证明常携带与原发性肿瘤相匹配的微卫星改变。本研究的目的是评估结直肠癌患者血清DNA微卫星的等位基因缺失和不稳定性的发生率。对27例结直肠腺癌患者术前血清和显微切割肿瘤中提取的DNA进行1号染色体短臂、5号染色体长臂、8号染色体短臂、12号染色体短臂、15号染色体长臂、17号染色体短臂、17号染色体长臂和18号染色体长臂上9个标记的基因分型。在所有肿瘤中，采用免疫组织化学方法检测MLH1和MSH2的表达。27个肿瘤中有26个（96%）以及27份血清样本中有16个（59%）存在包括杂合性缺失（LOH）或微卫星不稳定性（MSI）在内的微卫星改变。采用严格标准时，血清MSI比血清LOH更易检测到（p<0.02）。在肿瘤和血清DNA中存在高度MSI（超过两个不稳定位点）的3例患者中，有2例在免疫组织化学检测中显示MSH2阴性肿瘤。未发现肿瘤分期或临床结局与LOH或MSI类型的血清微卫星改变之间存在显著关联。尽管肿瘤的DNA释放表型仍有待阐明，但通过血清DNA微卫星分析对其进行检测似乎有助于肿瘤的诊断和监测，包括有或无MSI的结直肠癌。
