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Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

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  • Sudheer Kumar Gara

    (National Institutes of Health)

  • Justin Lack

    (National Institutes of Health)

  • Lisa Zhang

    (National Institutes of Health)

  • Emerson Harris

    (National Institutes of Health)

  • Margaret Cam

    (National Institutes of Health)

  • Electron Kebebew

    (National Institutes of Health
    Stanford University)

Abstract

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33 metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity among different metastatic sites in ACC and discovered recurrent mutations in several novel genes. We observed 37–57% overlap in genes that are mutated among different metastatic sites within the same patient. We also identified new therapeutic targets in recurrent and metastatic ACC not previously described in primary ACCs.

Suggested Citation

  • Sudheer Kumar Gara & Justin Lack & Lisa Zhang & Emerson Harris & Margaret Cam & Electron Kebebew, 2018. "Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06366-z
    DOI: 10.1038/s41467-018-06366-z
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