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Alexander Drilon, MD

Gregory J. Riely, MD, PhD


Genetic Alterations in Inflammatory Myofibroblastic Tumors

By: Lauren Harrison, MS
Posted: Friday, February 18, 2022

A group of researchers found multiple genetic alterations in inflammatory myofibroblastic tumors (IMFT), including NTRK fusions and mutations in ALK and PIK3CA, and correlated these mutations to clinical outcomes. This research was published in Clinical Cancer Research by Agnieszka Wozniak, PhD, of Katholieke Universiteit Leuven in Leuven, Belgium, and her colleagues.

The authors commented: “[These findings] 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.”

A total of 24 archived IMFT samples from the phase II CREATE trial, which studied the effects of crizotinib on patients with IMFT, were analyzed in this study. Researchers performed immunohistochemistry, fluorescence in situ hybridization, and whole-genome sequencing to look for copy-number alterations, gene fusions, and other mutations within the tumor tissue. These histologic and genetic findings were correlated with clinical outcomes and response to crizotinib.

Copy number alteration analysis and the mutational landscape of the IMFT samples showed extensive molecular heterogeneity. There were 12 ALK fusions with 11 different partners found in the IMFT samples. There were no tumors with rearrangements in ROS1 and none of the tumors had ROS1 expression on immunohistochemistry. One patient with ALK-negative disease who had a response to crizotinib was found to have an ETV6-NTRK fusion in their tumor. In addition, 58% showed loss of chromosome 22q, whereas 9% showed mutations in PIK3CA. There were recurrent focal alterations noted at 27 different loci.

Researchers correlated copy number alterations with progression-free survival and saw that chromosome 19 monosomy was associated with a shorter survival in patients receiving crizotinib (P = .008). Patients with PIK3CA mutations had shorter survival as well. Patients who responded to crizotinib had lower numbers of copy number alterations than nonresponders (12 vs. 30 regions).

Disclosure: For a full list of authors' disclosures, visit

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