NFATC2::NUTM2 Fusion Defines a Novel Primary Pulmonary Epithelial Tumor With a Distinctive Immunophenotype

Area of Science:

• Oncology
• Genomics
• Pathology

Background:

• Novel primary pulmonary epithelial tumors are increasingly identified with molecular techniques.
• The spectrum and pathological features of NFATC2::NUTM2 fusions in pulmonary tumors are not well-defined.

Purpose of the Study:

• To characterize the spectrum of NFATC2::NUTM2 fusions and associated pathological features in primary pulmonary tumors.
• To define a novel pulmonary tumor entity driven by NFATC2::NUTM2 fusions.

Main Methods:

• Integrated genomic analysis including high-throughput chromosome conformation capture (Hi-C) and RNA sequencing.
• Pathological assessment including histology, immunophenotyping, and ultrastructural examination.
• Clinical follow-up of patients after surgical resection.

Main Results:

• Six primary pulmonary tumors with recurrent NFATC2::NUTM2A/E fusions were identified.
• Tumors presented as peripheral lung nodules with a consistent immunophenotype (CK5/6+, GATA3+, calponin+, EMA+, DOG1+, p63-).
• All patients remained disease-free after complete resection.

Conclusions:

• NFATC2::NUTM2 fusions define a novel primary pulmonary tumor entity.
• This entity is characterized by a distinct immunophenotype and favorable prognosis.
• Multiomics approaches are crucial for characterizing rare neoplasms.