Biqiang Zheng1,2, Yueting Qu3, Jian Wang3, Yingqiang Shi1,2, Wangjun Yan4,2. 1. Department of Musculoskeletal Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China. 3. OrigiMed, Shanghai, P.R. China. 4. Department of Musculoskeletal Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China spinetumor@163.com.
Abstract
BACKGROUND/AIM: Undifferentiated pleomorphic sarcomas (UPSs) are difficult to treat, with a high recurrence rate. However, the genetic and molecular characterization of recurrent UPS has not been identified. PATIENTS AND METHODS: In this study, we investigated the pathogenic and targetable genetic alterations in 16 paired locally pre-recurrent and post-recurrent UPS cases by targeted next-generation sequencing (466 genes). RESULTS: Sequence variations were most frequently found in TP53 (66%), ATRX (34%), and RB1 (28%). In addition, for the first time, recurrent IL7R gene amplification (19%) and KMT2C gene mutation (16%) were detected in UPS. Interestingly, genetic alterations varied with tumor relapse. Importantly, targetable driver variants were found in recurrent UPS. Mutated genes were correlated with the cell cycle, PI3K/mTOR and RAS/MAPK signaling pathways. TMB was also found to be increased after tumor recurrence (4.6 vs. 7.5 mutations/MB, p=0.0343). CONCLUSION: Routine use of targeted next-generation sequencing for recurrent UPS can facilitate timely therapeutic decision-making. Copyright
BACKGROUND/AIM: Undifferentiated pleomorphic sarcomas (UPSs) are difficult to treat, with a high recurrence rate. However, the genetic and molecular characterization of recurrent UPS has not been identified. PATIENTS AND METHODS: In this study, we investigated the pathogenic and targetable genetic alterations in 16 paired locally pre-recurrent and post-recurrent UPS cases by targeted next-generation sequencing (466 genes). RESULTS: Sequence variations were most frequently found in TP53 (66%), ATRX (34%), and RB1 (28%). In addition, for the first time, recurrent IL7R gene amplification (19%) and KMT2C gene mutation (16%) were detected in UPS. Interestingly, genetic alterations varied with tumor relapse. Importantly, targetable driver variants were found in recurrent UPS. Mutated genes were correlated with the cell cycle, PI3K/mTOR and RAS/MAPK signaling pathways. TMB was also found to be increased after tumor recurrence (4.6 vs. 7.5 mutations/MB, p=0.0343). CONCLUSION: Routine use of targeted next-generation sequencing for recurrent UPS can facilitate timely therapeutic decision-making. Copyright
Authors: Yi Luo; Li Min; Yong Zhou; Fan Tang; Minxun Lu; Hongmei Xie; Yitian Wang; Hong Duan; Wenli Zhang; Chongqi Tu Journal: Medicine (Baltimore) Date: 2021-03-26 Impact factor: 1.817
Authors: Nuttavut Sumransub; Paari Murugan; Shelly Marette; Denis R Clohisy; Keith M Skubitz Journal: BMC Med Genomics Date: 2021-08-31 Impact factor: 3.063