{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dermawan JK"],"funding":["National Cancer Institute (NCI)","Suzie Wolf Coffland Fund","Cycle for Survival","National Cancer Institute","Kristin Ann Carr Foundation","NCI NIH HHS"],"pagination":["2260-2271"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11096044"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(10)"],"pubmed_abstract":["<h4>Purpose</h4>Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite recent large-scale genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model.<h4>Experimental design</h4>We performed comprehensive genomic profiling in a cohort of 195 soft tissue LMS (STLMS), 151 primary at presentation, and a control group of 238 uterine LMS (ULMS), 177 primary at presentation, with at least 1-year follow-up.<h4>Results</h4>In STLMS, French Federation of Cancer Centers (FNCLCC) grade but not tumor size predicted progression-free survival (PFS) or disease-specific survival (DSS). In contrast, in ULMS, tumor size, mitotic rate, and necrosis were associated with inferior PFS and DSS. In STLMS, a 3-tier genomic risk stratification performed well for DSS: high risk: co-occurrence of RB1 mutation and chr12q deletion (del12q)/ATRX mutation; intermediate risk: presence of RB1 mutation, ATRX mutation, or del12q; low risk: lack of any of these three alterations. The ability of RB1 and ATRX alterations to stratify STLMS was validated in an external AACR GENIE cohort. In ULMS, a 3-tier genomic risk stratification was significant for both PFS and DSS: high risk: concurrent TP53 mutation and chr20q amplification/ATRX mutations; intermediate risk: presence of TP53 mutation, ATRX mutation, or amp20q; low risk: lack of any of these three alterations. Longitudinal sequencing showed that most molecular alterations were early clonal events that persisted during disease progression.<h4>Conclusions</h4>Compared with traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS."],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma."],"pmcid":["PMC11096044"],"funding_grant_id":["P50 CA272170","P30 CA008748","LMS SPORE Career Enhancement Program","P50 CA217694"],"pubmed_authors":["Singer S","Hensley ML","Antonescu CR","Chiang S","Jadeja B","Maki RG","Dermawan JK","Tap WD","Movva S"],"additional_accession":[]},"is_claimable":false,"name":"Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma.","description":"<h4>Purpose</h4>Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite recent large-scale genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model.<h4>Experimental design</h4>We performed comprehensive genomic profiling in a cohort of 195 soft tissue LMS (STLMS), 151 primary at presentation, and a control group of 238 uterine LMS (ULMS), 177 primary at presentation, with at least 1-year follow-up.<h4>Results</h4>In STLMS, French Federation of Cancer Centers (FNCLCC) grade but not tumor size predicted progression-free survival (PFS) or disease-specific survival (DSS). In contrast, in ULMS, tumor size, mitotic rate, and necrosis were associated with inferior PFS and DSS. In STLMS, a 3-tier genomic risk stratification performed well for DSS: high risk: co-occurrence of RB1 mutation and chr12q deletion (del12q)/ATRX mutation; intermediate risk: presence of RB1 mutation, ATRX mutation, or del12q; low risk: lack of any of these three alterations. The ability of RB1 and ATRX alterations to stratify STLMS was validated in an external AACR GENIE cohort. In ULMS, a 3-tier genomic risk stratification was significant for both PFS and DSS: high risk: concurrent TP53 mutation and chr20q amplification/ATRX mutations; intermediate risk: presence of TP53 mutation, ATRX mutation, or amp20q; low risk: lack of any of these three alterations. Longitudinal sequencing showed that most molecular alterations were early clonal events that persisted during disease progression.<h4>Conclusions</h4>Compared with traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T12:36:49.564Z","creation":"2025-04-04T00:38:55.075Z"},"accession":"S-EPMC11096044","cross_references":{"pubmed":["38488807"],"doi":["10.1158/1078-0432.CCR-24-0148","10.1158/1078-0432.ccr-24-0148"]}}