Comprehensive Molecular Analysis of Inflammatory Myofibroblastic Tumors Reveals Diverse Genomic Landscape and Potential Predictive Markers for Response to Crizotinib.
Clin Cancer Res
; 27(24): 6737-6748, 2021 12 15.
Article
em En
| MEDLINE
| ID: mdl-34551905
ABSTRACT
PURPOSE:
The European Organization for Research and Treatment of Cancer (EORTC) clinical phase II trial 90101 "CREATE" showed high antitumor activity of crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT). However, recent findings suggested that other molecular targets in addition to ALK/ROS1 might also contribute to the sensitivity of this kinase inhibitor. We therefore performed an in-depth molecular characterization of archival IMFT tissue, collected from patients enrolled in this trial, with the aim to identify other molecular alterations that could play a role in the response to crizotinib. EXPERIMENTALDESIGN:
Twenty-four archival IMFT samples were used for histopathological assessment and DNA/RNA evaluation to identify gene fusions, copy-number alterations (CNA), and mutations in the tumor tissue. Results were correlated with clinical parameters to assess a potential association between molecular findings and clinical outcomes.RESULTS:
We found 12 ALK fusions with 11 different partners in ALK-positive IMFT cases by Archer analysis whereas we did not identify any ROS1-rearranged tumor. One ALK-negative patient responding to crizotinib was found to have an ETV6-NTRK fusion in the tumor specimen. The CNA profile and mutational landscape of IMFT revealed extensive molecular heterogeneity. Loss of chromosome 19 (25% of cases) and PIK3CA mutations (9% of cases) were associated with shorter progression-free survival in patients receiving crizotinib.CONCLUSIONS:
We identified multiple genetic alterations in archival IMFT material and provide further insight into the molecular profile of this ultra-rare, heterogeneous malignancy, which may potentially translate into novel treatment approaches for this orphan disease.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pulmonares
/
Neoplasias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article