4.5 Article

Brown Tumors Belong to the Spectrum of KRAS-driven Neoplasms

期刊

AMERICAN JOURNAL OF SURGICAL PATHOLOGY
卷 46, 期 11, 页码 1577-1582

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAS.0000000000001963

关键词

brown tumor; giant cell lesion; hyperparathyroidism; KRAS gene; RAS-MAPK pathway

资金

  1. Swiss National Science Foundation
  2. Foundation of the Bone Tumor Reference Centre
  3. Gertrude von Meissner Stiftung
  4. Stiftung fur krebskranke Kinder, Regio Basiliensis
  5. National Institute for Health Research
  6. Cancer Research UK University College London Experimental Cancer Medicine Centre
  7. RNOH Research and Development Department
  8. RNOH Biobank Team
  9. Tom Prince Trust

向作者/读者索取更多资源

Brown tumors are rare bone lesions associated with hyperparathyroidism. This study found that brown tumors may be true neoplasms driven by the activation of the RAS-MAPK signaling pathway. Regression of brown tumors after normalization of hyperparathyroidism suggests a second hit mediated by endocrine stimulation is required for tumor development. Brown tumors have a pathogenic relation to nonossifying fibroma and giant cell granuloma of the jaws.
Brown tumors are rare and generally self-limiting mass lesions of bone occurring in the context of hyperparathyroidism. Although commonly regarded as endocrine-driven tumor-like lesions, we detected pathogenic hotspot KRAS mutations in 10/16 brown tumors (62%) with similar frequencies found in cases affecting the peripheral and axial skeleton. Pathogenic mutations in other driver genes of the RAS-MAPK pathway were not identified. Our findings suggest brown tumors to represent true neoplasms driven by the activation of the RAS-MAPK signaling pathway. The frequent regression of brown tumors after normalization of hyperparathyroidism points to a second hit mediated by endocrine stimulation to be required for tumor development. Our findings underline the pathogenic relation of brown tumors to nonossifying fibroma and giant cell granuloma of the jaws which both appear histologically similar to brown tumors and are also driven by RAS-MAPK signaling pathway activation.

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