Kim Yoo Ri, Chung Nak Gyun, Kang Mi Ran, Yoo Nam Jin, Lee Sug Hyung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Tumori. 2010 Nov-Dec;96(6):1004-9.
Microsatellite instability (MSI) in sporadic gastric cancer (GC) and colorectal cancer (CRC) causes frameshift mutations in gene sequences that contribute to cancer pathogenesis. Many mutations have already been identified in these two cancer types, but some are still undiscovered.
We analyzed seven genes (cell cycle control and DNA damage signaling/repair-related genes) with seven or more mononucleotide repeats in 30 GC samples with high MSI (MSI-H), 15 GC samples with low MSI (MSI-L), 45 GC samples that were microsatellite stable (MSS), 33 CRC samples with MSI-H, 15 CRC samples with MSI-L, and 45 CRC samples that were MSS. Single-strand conformation polymorphism (SSCP) and DNA sequencing were used for the analysis.
We found somatic frameshit mutations of the KNTC1 (6.7% GC, 12.1% CRC), ZC3H13 (3.3% GC, 15.2% CRC), CENPH (6.7% GC), TOPBP1 (3.0% CRC), NDCO80 (3.0% CRC), RIF1 (6.7% GC), and NBS1 (3.3% GC, 3.0% CRC) genes in the cancers with MSI-H. Mutations were detected in MSI-H, but not in MSI-L or MSS samples.
Novel frameshift mutations occurred in seven genes in GC and CRC with MSI-H. The results of our study suggest that the mutations might contribute to the development of GC and CRC with MSI by deregulation of the cell cycle and DNA damage signaling/repair.
散发性胃癌（GC）和结直肠癌（CRC）中的微卫星不稳定性（MSI）会导致基因序列中的移码突变，这有助于癌症的发病机制。在这两种癌症类型中已经发现了许多突变，但仍有一些未被发现。
我们分析了30个高微卫星不稳定性（MSI-H）的GC样本、15个低微卫星不稳定性（MSI-L）的GC样本、45个微卫星稳定（MSS）的GC样本、33个MSI-H的CRC样本、15个MSI-L的CRC样本和45个MSS的CRC样本中的7个基因（细胞周期控制和DNA损伤信号传导/修复相关基因），这些基因具有七个或更多的单核苷酸重复序列。采用单链构象多态性（SSCP）和DNA测序进行分析。
我们在MSI-H的癌症中发现了KNTC1（6.7%的GC，12.1%的CRC）、ZC3H13（3.3%的GC，15.2%的CRC）、CENPH（6.7%的GC）、TOPBP1（3.0%的CRC）、NDCO80（3.0%的CRC）、RIF1（6.7%的GC）和NBS1（3.3%的GC，3.0%的CRC）基因的体细胞移码突变。在MSI-H样本中检测到了突变，但在MSI-L或MSS样本中未检测到。
MSI-H的GC和CRC中有七个基因发生了新的移码突变。我们的研究结果表明，这些突变可能通过细胞周期和DNA损伤信号传导/修复的失调，促进MSI的GC和CRC的发展。
