A somatic activating KRAS variant identified in an affected lesion of a patient with Gorham–Stout disease

Akifumi Nozawa, Michio Ozeki, Tetsuya Niihori, Natsuko Suzui, Tatsuhiko Miyazaki, Yoko Aoki

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Gorham–Stout disease (GSD), a rare disorder of unknown etiology, is characterized by massive osteolysis that is associated with proliferation and dilation of lymphatic vessels. Variants in cancer-associated genes have been described in complex lymphatic anomalies. To explore the pathogenesis of GSD, we performed the amplicon-based deep sequencing on 50 cancer-related genes to assay affected tissues from the six patients with GSD. In one patient, a somatic activating KRAS c.182A > G variant (p.Q61R) was detected in 1% of the tissue sample. Conversely, the mutant allele was not detected in uninvolved normal skin and blood samples. Histopathology of the patient’s tissue sample showed proliferation of abnormal lymphatic and blood vascular endothelial cells, osteoclasts, and activated macrophages. The activating KRAS variant is a known ‘hotspot’ variant, frequently identified in several types of human cancer. This is the first report of identifying a pathogenic variant in a patient with GSD. This finding may set the stage for elucidation of pathophysiology and the development of novel therapies for GSD.

Original languageEnglish
Pages (from-to)995-1001
Number of pages7
JournalJournal of Human Genetics
Volume65
Issue number11
DOIs
Publication statusPublished - 2020 Nov 1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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