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|Ref Type||Journal Article|
|Authors||Kasper B, Gruenwald V, Reichardt P, Bauer S, Hohenberger P, Haller F|
|Title||Correlation of CTNNB1 Mutation Status with Progression Arrest Rate in RECIST Progressive Desmoid-Type Fibromatosis Treated with Imatinib: Translational Research Results from a Phase 2 Study of the German Interdisciplinary Sarcoma Group (GISG-01).|
|Journal||Annals of surgical oncology|
|Abstract Text||CTNNB1 gene mutations are the molecular key events in the majority of sporadic desmoid-type fibromatosis (DF). The specific S45F mutation has been reported to be associated with a more aggressive clinical course in DF. For the current study, the CTNNB1 mutation status was analyzed in DF samples from the prospective German Interdisciplinary Sarcoma Group (GISG) phase 2 study evaluating imatinib to induce progression arrest in DF Response Evaluation Criteria In Solid Tumors (RECIST) progressive patients.Thirty-seven patients were treated with a planned dose of imatinib 800 mg daily over 2 years (NCT01137916). The progression arrest rate (PAR) after 6 months of treatment was the primary endpoint of the study. CTNNB1 exon 3 mutation status was analyzed using Sanger sequencing.Thirty-three (97 %) of 34 patients reaching the primary endpoint were evaluable for CTNNB1 mutation exon 3 status. T41A mutations accounted for 30.3 % of the study samples and S45 mutations for 48.5 %, whereas CTNNB1 wild-type status was found in 21.2 %. The respective PAR at 6 months was 70, 81, and 43 %. Patients harboring CTNNB1 mutations demonstrated a higher PAR compared to wild-type DF. There was a statistically significant difference comparing patients with S45F mutations (85 % PAR) versus wild-type status (p = 0.05).Mutations at position S45 were overrepresented in the GISG-01 trial recruiting RECIST progressive patients only. The positive correlation of CTNNB1 mutation status with the progression arrest rate after imatinib therapy supports the idea of a potential predictive impact of the mutation status on DF treatment decision making.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|CTNNB1 T41A||desmoid tumor||sensitive||Imatinib||Clinical Study - Cohort||Actionable||In a retrospective analysis, patients with desmoid fibromatosis harboring CTNNB1 T41A demonstrated a greater progression arrest rate at 6 months (70%) compared to patients with CTNNB1 wild-type (45%) when treated with Gleevec (imatinib) (PMID: 26861905).||26861905|
|CTNNB1 S45F||desmoid tumor||sensitive||Imatinib||Clinical Study - Cohort||Actionable||In a retrospective analysis, patients with desmoid fibromatosis harboring CTNNB1 S45F demonstrated a greater progression arrest rate at 6 months compared to CTNNB1 wild-type patients (85% vs 43%, p=0.05) when treated with Gleevec (imatinib) (PMID: 26861905).||26861905|
|CTNNB1 act mut||desmoid tumor||sensitive||Imatinib||Clinical Study - Cohort||Actionable||In a retrospective analysis, patients with desmoid fibromatosis harboring CTNNB1 activating exon 3 mutations demonstrated a greater progression arrest rate at 6 months compared to patients with CTNNB1 wild-type tumor when treated with Gleevec (imatinib) (PMID: 26861905).||26861905|