The oncologist · 2025
Clinicopathological characteristics of progressive gastrointestinal stromal tumors and heterogeneity analyses of secondary mutations.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Jiaxin, Sun Lin, Liu Shasha, Liu Huimin, Li Bin, Zhan Hongjie, Sun Yan
Аннотация
BACKGROUND: Although there have been multiple lines of drugs for gastrointestinal stromal tumors (GISTs), the drug response depends on the progressive tumors' biological behaviors and secondary mutations.
METHODS: We investigated the primary and secondary mutations in multiple tumors from the same patients and at multiple regions from the same tumor to analyze the inter- and intratumoral heterogeneities using Sanger sequencing and next-generation sequencing (NGS).
RESULTS: Secondary mutations were more frequently detected in patients with a targeted therapy history and who continued their targeted therapy until surgery or biopsy, in larger tumors, and in tumors located in the intestine, abdominal cavity, and mesentery. Secondary mutations were detected in only 57.5% of the samples from the cases with secondary mutations, and 34.8% of the cases presented multiple types of secondary mutations, including both intertumoral and intratumoral heterogeneities. Temporal heterogeneity was also observed at different time points of progression. The results of NGS and Sanger sequencing were consistent for the individual sample, but Sanger sequencing detected multiple types of secondary mutations from different tumors of the same patient. Liquid biopsy also only detected partial secondary mutations revealed by Sanger sequencing.
CONCLUSION: Progressive GISTs had intertumoral and intratumoral heterogeneities of secondary mutations. Sanger sequencing had its own advantage in revealing the heterogeneity of secondary mutations. The improvement in the detection rate of secondary mutations by selecting the appropriate tumor sample to be tested, or even the appropriate tumor region or test method, is helpful to identify the optimal drugs for progressive GISTs.
METHODS: We investigated the primary and secondary mutations in multiple tumors from the same patients and at multiple regions from the same tumor to analyze the inter- and intratumoral heterogeneities using Sanger sequencing and next-generation sequencing (NGS).
RESULTS: Secondary mutations were more frequently detected in patients with a targeted therapy history and who continued their targeted therapy until surgery or biopsy, in larger tumors, and in tumors located in the intestine, abdominal cavity, and mesentery. Secondary mutations were detected in only 57.5% of the samples from the cases with secondary mutations, and 34.8% of the cases presented multiple types of secondary mutations, including both intertumoral and intratumoral heterogeneities. Temporal heterogeneity was also observed at different time points of progression. The results of NGS and Sanger sequencing were consistent for the individual sample, but Sanger sequencing detected multiple types of secondary mutations from different tumors of the same patient. Liquid biopsy also only detected partial secondary mutations revealed by Sanger sequencing.
CONCLUSION: Progressive GISTs had intertumoral and intratumoral heterogeneities of secondary mutations. Sanger sequencing had its own advantage in revealing the heterogeneity of secondary mutations. The improvement in the detection rate of secondary mutations by selecting the appropriate tumor sample to be tested, or even the appropriate tumor region or test method, is helpful to identify the optimal drugs for progressive GISTs.