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Landscape of an Enigma

May 29, 2013

Adenoid cystic carcinomaA NIDCR-supported researcher and colleagues have published online in the journal Nature Genetics, the first comprehensive snapshot of the mutational landscape of adenoid cystic carcinoma (ACC) of the salivary glands. These tumors are among the most enigmatic of human malignancies and represent about 10 percent of head and neck cancer. In the paper, the scientists sequenced 55 exomes (the complete set of protein-coding sequences in a DNA sample) and five genomes (the complete set of genes in a DNA sample) from 60 ACC tumors. Among the many novel discoveries arising from these more detailed, next-generation sequencing technologies, the researchers report:

  • ACC has a lower rate of exonic somatic mutations than other solid tumors. The researchers identified a mean of 22 somatic mutations per ACC sample, compared to a recent report, for example, of 130 coding mutations on average per head and neck cancer sample.
  • A majority (57 percent) of ACCs have a chromosomal translocation of the MYB proto-oncogene and the transcription factor gene NFIB. This translocation, or crossing of the two chromosomes, creates the abnormal fusion oncogene gene, MYB-NFIB, which appears to be a common pro-growth driver of the cancer. Previous studies identified the translocation, and the current work confirms these reports.
  • Enrichment, or clustering, of mutations in genes that align in specific cell signaling pathways. These pathways include the remodeling of chromatin in the nucleus, responses to DNA damage, signaling involving the abnormal MYB-MYC oncogene, and protein kinase A and phosphatidyl inosital 3-kinase (PI3K). The latter helps to initiate several basic cell functions, such as the polymerization of actin (important for cell motility and division), assembling signal complexes, and priming protein kinase signaling cascades.
  • Recurrent deletions on chromosomes 6q24, 12q13 and 14q and the identification of several potential therapeutic targets (histone acetyl transferases, FGFR, and MYB).

Looking further down the research road, the authors concluded that their data provide a much-needed genetic framework to characterize the molecular changes that drive ACC. Given its comprehensive overview of the genetic landscape, the study also provides the scientific basis to identify new and potentially more effective targets for therapy.

The study is titled “The mutational landscape of adenoid cystic carcinoma.” It is published online on May 19 in Nature Genetics. The authors include Allen S. Ho, Kasthuri Kannan, William Lee, Timothy A. Chan, et al.

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This page last updated: February 26, 2014