AbstractAdenoid Cystic Carcinoma of the Lacrimal Gland: MYB Gene Activation, Genomic Imbalances, and Clinical Characteristics Purpose: To investigate genetic alterations in lacrimal gland adenoid cystic carcinomas (ACC) in relation to clinical data and survival. Methods: The expression and identity of MYB‐NFIB fusion transcripts were studied using RT‐PCR and nucleotide sequence analyses. Q‐PCR and immunohistochemistry were used to evaluate the expression of MYB and MYB‐NFIB target genes. High‐resolution array‐based comparative genomic hybridization (arrayCGH) and FISH were used to study copy number alterations and MYB rearrangements. Results: The median age of the patients were 43 years and the median time of survival was 8.6 years. The MYB‐NFIB fusion was expressed in 7/14 ACCs. All non‐ACC tumors were fusion‐negative. All 13 ACCs tested stained positive for the MYB protein and for the MYB targets KIT and BCL2, 12 were positive for MYC and CCNE1, and nine for CCNB1. Rearrangements of MYB were detected in 8/13 cases. ArrayCGH analysis revealed recurrent copy number alterations with losses involving 6q23‐q27, 12q12‐q14.1, 17p13.3‐p12 and gains involving 19q12, 19q13.31‐qter, 8q24.13‐q24.21, 11q12.3‐q14.1, and 6q23.3. Neither MYB‐NFIB fusion nor any copy number alteration correlated with survival. Conclusions: Lacrimal gland ACCs are genetically and clinically similar to their salivary gland counterparts and MYB‐NFIB is a useful biomarker for ACC. Our data also suggests that MYB and its downstream targets are potential therapeutic targets for these tumors.