Rearrangements, Expression, and Clinical Significance of MYB and MYBL1 in Adenoid Cystic Carcinoma: A Multi-Institutional Study.

Adenoid cystic carcinoma (ACC) is an aggressive head and neck malignancy characterized by a t (6;9) translocation resulting in an gene fusion or, more rarely, an fusion. The true frequency and clinical significance of these alterations are still unclear. Here, we have used tissue microarrays and analyzed 391 ACCs and 647 non-ACC salivary neoplasms to study the prevalence, expression, and clinical significance of alterations by FISH and immunohistochemistry. Alterations of or were found in 78% of the cases, of which 62% had alterations and 16% had rearrangements. Overexpression of MYB/MYBL1 oncoproteins was detected in 93% of the cases. split signal, seen in 39% of the cases, was specific for ACC and not encountered in non-ACC salivary tumors. Loss of the 3'-part of was enriched in grade 3 tumors and was a significant independent prognostic biomarker for overall survival in multivariate analyses. We hypothesize that loss of the 3'-part of results from an unbalanced t(6;9) leading to an fusion with concomitant loss of the segment distal to the breakpoint in 6q23.3. Our study provides new knowledge about the prevalence and clinical significance of alterations and indicates the presence of genes with tumor suppressive functions in 6q23.3-qter that contribute to poor prognosis and short overall survival in ACC.