Fridrichová I, Ilencíková D, Friedl W, Hlavcák P, Skorvaga M, Krizan P, Pálaj J, Pirsel M, Farkasová E, Bartosová Z
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
Neoplasma. 2000;47(4):219-26.
Patients with hereditary non-polyposis colorectal cancer (HNPCC) have a DNA mismatch repair defect (MMR) in their tumor tissue that results in instability of microsatellite DNA sequences (MSI). Thus, MSI analysis may effectively indicate this form of cancer that should be then proved by analysis of germline mutations in MMR genes. The aim of this study was to identify HNPCC suspected patients in the Slovak population by investigating microsatellite instability in colorectal tumor tissues. MSI was studied at 5-11 loci in matched tumor and normal DNA using radioactively labeled PCR products separated on sequencing gels. High microsatellite instability (MSI-H) was present only in patients younger than 50 years, in 100% of patients having two affected relatives by colorectal cancer and in 67% of patients with only one affected relative. In both groups of patients colorectal cancer was present in two successive generations. No MSI-H was found in the group of patients older than 50 years, even if they had positive family history for colorectal cancer. Among all markers used, the BAT26 mononucleotide repeat (100%), DI0S197 and D13S175 (62.5%) dinucleotide repeats were the most frequently altered in the tumor tissues. Retrospective analysis revealed that some of the patients having MSI-H tumors have had clinicopathological characteristics frequently reported to HNPCC. The family members of those patients with MSI-H are enrolled in preventive health care program until mutational analyses will enable to select carriers from non-carriers of mutated MMR genes.
遗传性非息肉病性结直肠癌（HNPCC）患者的肿瘤组织存在DNA错配修复缺陷（MMR），这导致微卫星DNA序列（MSI）不稳定。因此，MSI分析可有效指示这种癌症形式，随后应通过MMR基因种系突变分析加以证实。本研究的目的是通过调查结直肠肿瘤组织中的微卫星不稳定性，在斯洛伐克人群中识别疑似HNPCC患者。使用在测序凝胶上分离的放射性标记PCR产物，在匹配的肿瘤和正常DNA中的5 - 11个位点研究MSI。高微卫星不稳定性（MSI-H）仅存在于年龄小于50岁的患者中，在100%有两个患结直肠癌亲属的患者以及67%仅有一个患结直肠癌亲属的患者中出现。在这两组患者中，结直肠癌在两代人中均有出现。在年龄大于50岁的患者组中未发现MSI-H，即使他们有结直肠癌的阳性家族史。在所有使用的标记中，BAT26单核苷酸重复序列（100%）、DI0S197和D13S175二核苷酸重复序列（62.5%）在肿瘤组织中最常发生改变。回顾性分析显示，一些具有MSI-H肿瘤的患者具有一些常被报道与HNPCC相关的临床病理特征。那些具有MSI-H的患者的家庭成员已纳入预防性医疗保健计划，直到突变分析能够从携带突变MMR基因的个体中筛选出非携带者。
