Mutation signature of adenoid cystic carcinoma: evidence for transcriptional and epigenetic reprogramming
Henry F. Frierson Jr., Christopher A. Moskaluk
Henry F. Frierson Jr., Christopher A. Moskaluk
Published June 17, 2013
Citation Information: J Clin Invest. 2013;123(7):2783-2785. https://doi.org/10.1172/JCI69070.
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Mutation signature of adenoid cystic carcinoma: evidence for transcriptional and epigenetic reprogramming

Abstract

Adenoid cystic carcinoma (ACC), a relatively rare malignancy usually of salivary gland origin, has a signature v-myb avian myeloblastosis viral oncogene homolog–nuclear factor I/B (MYB-NFIB) gene fusion that activates MYB transcriptional regulatory activity. A new study in this issue by Stephens et al. is a comprehensive genomic mutation profiling analysis of this neoplasm and documents a common theme of alteration in chromatin regulatory genes. Also, mutations in SPEN (split ends, homolog of Drosophila), which encodes an RNA-binding coregulatory protein, suggest that other changes in transcriptional regulation may involve the NOTCH, FGFR, or other signaling pathways in which SPEN participates. Since there is a low prevalence of mutations in common oncogenes and tumor-suppressor genes, it is likely that alterations primarily in specific transcriptional regulatory genes, augmented by changes in chromatin structure, drive the neoplastic process in ACC.

Authors

Henry F. Frierson Jr., Christopher A. Moskaluk

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Figure 1

The neoplastic transformation of normal salivary gland (upper histologic figure) to adenoid cystic carcinoma (lower histologic figure) is the culmination of genetic alterations including translocation, deletions, and mutations, catalogued from comprehensive array CHG (4) and whole exome sequencing (1) analyses.

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The neoplastic transformation of normal salivary gland (upper histologic...
Key targets include the activation of MYB, most commonly by a t(6;9) chromosomal translocation (karyotype shown) and mutations in genes that regulate chromatin structure (shown graphically). Original magnification, ×400 (upper panel); ×200 (lower panel).