关键词: hypermutability microsatellite instability (MSI) short tandem repeats (STRs) tumors

Mesh : Biomarkers, Tumor / genetics Breast Neoplasms / genetics pathology Carcinoma, Renal Cell / genetics pathology Colorectal Neoplasms / genetics pathology DNA, Neoplasm / genetics Esophageal Neoplasms / genetics pathology Female Frameshift Mutation / genetics Humans Liver Neoplasms / genetics pathology Lung Neoplasms / genetics pathology Microsatellite Instability Microsatellite Repeats / genetics Neoplasms / classification genetics Pancreatic Neoplasms / genetics pathology Stomach Neoplasms / genetics pathology

来  源:   DOI:10.3390/genes12020197   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
A growing number of studies have shown immunotherapy to be a promising treatment strategy for several types of cancer. Short tandem repeats (STRs) have been proven to be alternative markers for the evaluation of hypermutability in gastrointestinal (GI) cancers. However, the status of STRs and microsatellite instability (MSI) in other tumors have not yet been investigated. To further compare STR and MSI alterations in different tumors, a total of 407 paired DNAs were analyzed from the following eight tumor types: breast cancer (BC), hepatocellular cancer (HCC), pancreatic cancer (PC), colorectal cancer (CRC), gastric cancer (GC), lung cancer (LC), esophageal cancer (EC), and renal cell cancer (RCC). The STR alteration frequencies varied in different tumors as expected. Interestingly, none of the patients possessed MSI-low (MSI-L) or MSI-high (MSI-H), except for the GI patients. The highest STR alteration was detected in EC (77.78%), followed by CRC (69.77%), HCC (63.33%), GC (54.55%), LC (48.00%), RCC (40.91%), BC (36.11%), and PC (25.71%). The potential cutoff for hypermutability was predicted using the published objective response rate (ORR), and the cutoff of LC and HCC was the same as that of GI cancers (26.32%). The cutoffs of 31.58% and 10.53% should be selected for BC and RCC, respectively. In summary, we compared MSI and STR status in eight tumor types, and predicted the potential threshold for hypermutability of BC, HCC, CRC, GC, LC, EC, and RCC.
摘要:
越来越多的研究表明,免疫疗法是几种癌症的有希望的治疗策略。短串联重复序列(STR)已被证明是评估胃肠道(GI)癌症超突变性的替代标记。然而,其他肿瘤中STRs和微卫星不稳定性(MSI)的状态尚未得到研究.为了进一步比较不同肿瘤中的STR和MSI改变,总共分析了以下八种肿瘤类型的407个配对DNA:乳腺癌(BC),肝细胞癌(HCC),胰腺癌(PC),结直肠癌(CRC),胃癌(GC),肺癌(LC),食管癌(EC),肾细胞癌(RCC)。如预期的,STR改变频率在不同肿瘤中变化。有趣的是,没有患者具有MSI低(MSI-L)或MSI高(MSI-H),除了胃肠道患者。在EC中检测到最高的STR改变(77.78%),其次是CRC(69.77%),HCC(63.33%),GC(54.55%),LC(48.00%),RCC(40.91%),BC(36.11%),和PC(25.71%)。使用已发布的客观反应率(ORR)预测超可变性的潜在截止值,LC和HCC的临界值与GI癌相同(26.32%)。BC和RCC应选择31.58%和10.53%的截止值。分别。总之,我们比较了8种肿瘤类型的MSI和STR状态,并预测了BC超突变的潜在阈值,HCC,CRC,GC,LC,EC,和RCC。
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