Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma.
Clin Cancer Res
; 30(10): 2260-2271, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38488807
ABSTRACT
PURPOSE:
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. EXPERIMENTALDESIGN:
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.RESULTS:
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.CONCLUSIONS:
Compared with traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Uterinas
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Genômica
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Leiomiossarcoma
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article