Detecting Rare ALK Gene Fusions in Unclassified Spindle Cell Lung Tumors Using Anchored Multiplex PCR/Targeted RNA...

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• Pulmonary spindle cell tumors are aggressive with few systemic treatment options.
• Conventional fusion assays may miss novel or atypical gene rearrangements.
• Actionable genomic alterations are present in a subset of these tumors.

Purpose of the Study:

• To systematically investigate oncogenic fusions in pulmonary spindle cell tumors.
• To identify novel ALK fusion partners using anchored multiplex PCR-based targeted RNA sequencing.
• To evaluate the utility of ALK immunohistochemistry for screening.

Main Methods:

• Analysis of 11 surgically resected pulmonary spindle cell tumors.
• Anchored multiplex PCR-based targeted RNA sequencing using the FusionPlex Sarcoma panel.
• Supplementation with custom primers for RET, NTRK1, NTRK2, and NRG1.

Main Results:

• Two tumors (18.2%) harbored ALK fusions: PPFIBP1::ALK and SYCL3::ALK.
• Both ALK-fusion positive tumors showed positive ALK immunohistochemical staining.
• Morphologic heterogeneity was observed in ALK-rearranged tumors.

Conclusions:

• This study expands the molecular spectrum of pulmonary spindle cell tumors.
• ALK immunohistochemistry is a valuable screening tool for these rare tumors.
• Anchored multiplex PCR-based RNA sequencing is effective for detecting therapeutically relevant fusions, including those with uncommon partners.