Zheng Yanying, Chen Jie, Zhang Xiang, Xie Ling, Zhang Yifen, Sun Yi
Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Department of Pathology, No.155 Hanzhong Road, 210029 Nanjing, China.
Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Department of Pathology, No.155 Hanzhong Road, 210029 Nanjing, China.
Bull Cancer. 2020 Nov;107(11):1091-1097. doi: 10.1016/j.bulcan.2020.08.001. Epub 2020 Sep 23.
This study aims to analyze sensitivities and polymorphisms of the Bethesda panel markers (BAT25, BAT26, D2S123, D5S346 and D17S250) for microsatellite instability testing in Chinese from Jiangsu Province and their clinical implication.
MSI, sensitivity and polymorphism analysis in 541 colorectal cancer (CRC) patients were detected by fragment analysis.
Five hundred and twenty-five tissue samples and 541 blood samples of the 541 sample pairs were successfully amplified. Thirty-four (6.5%) cases were MSI-high (MSI-H) while 33 (6.3%) and 458 (87.2%) were MSI-low (MSI-L) and microsatellite stable (MSS), respectively. BAT26 (85.3%) exhibited the highest instability followed by BAT25 (82.4%), D2S123 (67.6%), D17S250 (64.7%) and D5S346 (50.0%) in MSI-H cases. The median ages of CRC patients with LS, MSI-H, MSI-L and MSS status were 38-43, 48, 60 and 63, respectively. 75.0%, 44.1%, 12.1% and 7.0% CRC cases were mucinous carcinomas in LS, MSI-H, MSI-L and MSS group, respectively. For D2S123, D17S250 and D5S346, heterozygosity was 80.8%, 74.1% and 57.7% and sizes of polymorphic variation range (PVR) were 207bp to 234bp, 140bp to 169bp and 109bp to 137bp, respectively. For D2S123 and D5S346, there was a bimodal distribution distinguishing the D17S250 from an indistinct trimodal or tetramodal distribution.
MSI-H cases showed earlier onset and higher proportion of mucinous carcinomas. Mononucleotide BAT26 and BAT25 exhibited higher sensitivity than dinucleotides D2S123, D17S250 and D5S346 in the Chinese population. The dinucleotide markers were highly polymorphic with high percent of heterozygosity, great variation in repeat length and non-normal distribution in Chinese population from Jiangsu Province.
本研究旨在分析江苏省中国人群中用于微卫星不稳定性检测的贝塞斯达面板标记物（BAT25、BAT26、D2S123、D5S346和D17S250）的敏感性和多态性及其临床意义。
通过片段分析检测541例结直肠癌（CRC）患者的微卫星不稳定性、敏感性和多态性。
541对样本中的525个组织样本和541个血液样本成功扩增。34例（6.5%）为微卫星高度不稳定（MSI-H），33例（6.3%）为微卫星低度不稳定（MSI-L），458例（87.2%）为微卫星稳定（MSS）。在MSI-H病例中，BAT26（85.3%）表现出最高的不稳定性，其次是BAT25（82.4%）、D2S123（67.6%）、D17S250（64.7%）和D5S346（50.0%）。林奇综合征（LS）、MSI-H、MSI-L和MSS状态的CRC患者的中位年龄分别为38 - 43岁、48岁、60岁和63岁。LS、MSI-H、MSI-L和MSS组中黏液腺癌的CRC病例分别占75.0%、44.1%、12.1%和7.0%。对于D2S123、D17S250和D5S346，杂合度分别为80.8%、74.1%和57.7%，多态性变异范围（PVR）大小分别为207bp至234bp、140bp至169bp和109bp至137bp。对于D2S123和D5S346，存在双峰分布，将D17S250与不明显的三峰或四峰分布区分开来。
MSI-H病例发病较早，黏液腺癌比例较高。在中国人群中，单核苷酸BAT26和BAT25比二核苷酸D2S123、D17S250和D5S346表现出更高的敏感性。二核苷酸标记物具有高度多态性，杂合度高，重复长度变化大，在江苏省中国人群中呈非正态分布。
