Targetable Alterations in Adult Patients With Soft-Tissue Sarcomas: Insights for Personalized Therapy.

ABSTRACT: Importance:Patients with advanced soft-tissue sarcomas (STS) have a median overall survival of less than 18 months. Identification of molecular abnormalities for which targeted therapies are available or can be developed is critical for improving patient outcomes. Objective:To characterize targetable genomic alterations (GAs) in patients with STS. Design, Setting, and Participants:This cross-sectional study of next-generation sequencing results from 584 patients with STS included in the AACR GENIE Database. Main Outcomes and Measures:Presence of targetable GAs in STS. Results:Of 584 patients included in the analysis, 294 (50.3%) were men and 290 (49.7%) were women, with a median age of 56 years (range, 18-89 years). There were 331 (57%) patients with complex genomics sarcomas, 144 (25%) with translocation-related sarcomas, and 112 (18%) with other sarcomas (inactivating mutation, simple amplicon). A total of 2697 alterations were identified in 451 genes (1154 substitutions, 765 gene amplifications, 364 short indels and splicing variants, 346 gene homozygous deletions, and 68 gene rearrangements) with a median of 4 (1-53) per case. In order of frequency, the 20 genes most often altered were: TP53, MDM2, CDK4, RB1, ATRX, CDKN2A, PTEN, NF1, CDKN2B, KMT2D, GLI1, ATM, TERT, PI3KCA, NOTCH1, MAP2K4, ERBB4, ARID1A, TSC2, and TNFAIP3. At least 1 targetable GA was found in 239 cases (41%) with a statistically significant higher number in other and complex genomics sarcomas than in translocation-related sarcomas (respectively other: n=89, 82%, complex: n = 131, 40%, translocation: n = 19, 13%; ?2 test, P?

SUBMITTER: Lucchesi C 

PROVIDER: S-EPMC6233783 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature