Molecular variations in uterine carcinosarcomas identify therapeutic opportunities.
Int J Gynecol Cancer
; 30(4): 480-484, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-32114514
ABSTRACT
OBJECTIVE:
To perform comprehensive genomic profiling on a large cohort of patients with uterine carcinosarcomas to identify potential therapeutic targets.METHODS:
Molecular profiling was conducted on 168 retrospectively de-identified patients with uterine carcinosarcomas using the Caris Life Sciences platform. Specimens were evaluated for aberrations in protein expression by immunohistochemistry, DNA sequence mutation using a 592-gene next generation sequencing panel, copy number amplification using next generation sequencing or in situ hybridization, and fusion events using NextGen RNA sequencing. Tumor mutational load and microsatellite instability were also evaluated.RESULTS:
We identified 168 patients with uterine carcinosarcoma; median age of the cohort was 67 years. The most common mutations were observed in the following genes TP53 (86%), PIK3CA (34%), FBXW7 (23%), PTEN (18%), KRAS (16%), PPP2R1A (10%). Tumor mutational load was low to moderate in most cases (50% and 45%, respectively). HER2/neu (ERBB2) was amplified in 9% of tumors. Immunohistochemistry protein expression was elevated in TOP2A (95%), TS (80%), PTEN (76%), and TUBB3 (66%). Mismatch repair deficiency was rare (4%).CONCLUSIONS:
Multiple somatic mutations and copy number alterations in genes that are therapeutic targets were identified in half of cases. Uterine carcinosarcomas represent an aggressive histology with limited treatment options and poor outcomes, and clinical trials are needed to validate new therapeutic targets.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Uterinas
/
Carcinosarcoma
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
Idioma:
En
Revista:
Int J Gynecol Cancer
Asunto de la revista:
GINECOLOGIA
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos