NUT midline carcinoma is an aggressive neoplasm defined by chromosomal rearrangements of the nuclear protein in testis (NUT) gene (NUTM1). In this article, we present a strategy to detect this rare tumor through a standard DNA methylation array analysis even when occurring in unusual anatomic sites. We illustrate our approach through a case study in which we detected metastatic spread of a NUT midline carcinoma within a bone marrow biopsy that exhibited histological features of a blastoid, undifferentiated neoplasm. Our strategy builds on molecular data derived from The Cancer Genome Atlas and Gene Expression Omnibus as well as computational strategies adopted from the Brain Tumor Methylation Classifier. It is a combined approach that detects the unusual cell lineage of NUT midline carcinomas and makes diagnostic use of the entity-specific copy number alterations.
Keywords: Copy number variation profile; DNA methylation profile; Machine learning; NUT midline carcinoma.