Raymond Tu

We have a research interest in relating imaging with genomics. Our brief review article, “Genetics of Von Hippel-Lindau Disease,” is an educational review for the radiologist to help link genotypes with imaging phenotypes.

Von Hippel-Lindau (VHL) disease is particularly interesting in that both molecular genetic sequencing and imaging play crucial roles in disease diagnosis and surveillance. Patients with VHL disease have an inactivating germline mutation in 1 copy of the VHL gene and 1 normally functioning wild type allele.

David Dwyer

Tumor development depends on mutation of the remaining wild type allele in a susceptible target organ.1 The VHL gene product is a tumor-suppressor protein that influences many cellular pathways, but ultimately allows for the inappropriate overproduction of hypoxia-inducible messenger RNAs and unregulated cell growth.2-4 Imaging plays a crucial role, particularly in the identification of CNS hemangioblastomas. These are the most common tumors in VHL disease, affecting 60%– 80% of all patients, and are the presenting features in approximately 40% of patients. Screening is critical in all patients with VHL (both within and outside of the CNS) because lesions are treatable.1 Indeed, imaging and genetics may inform each other, as suspicion for VHL based on one modality often prompts obtaining the other.

As the revolution in molecular biology that occurred in the 20th century has provided the tools to understand disease at the molecular level, carrying on into the 21st century will be genetic advances to define specific therapies for the individual. This era of precision medicine will include the radiologist to reconcile genotype and phenotype, ultimately improving the diagnostic utility of noninvasive medical imaging. While our future work will hopefully include original research, we will continue to work on educational reviews to create familiarity with the vocabulary of genetic pathways. It is our hope that the continued relation of imaging with genomics will improve clinical decision-making and patient outcomes.

References

1. Franke G, Bausch B, Hoffmann MM, et al. Alu-Alu recombination underlies the vast majority of large VHL germline deletions: molecular characterization and genotype-phenotype correlations in VHL patients. Hum Mutat 2009;30:776–86.
2. Latif F, Tory K, Gnarra J, et al. Identification of the von Hippel- Lindau disease tumor suppressor gene. Science 1993;260:1317–20.
3. Shanbhogue KP, Hock M, Fatterpaker G, et al. Von Hippel-Lindau disease: review of genetics and imaging. Radiol Clin North Am 2016;54:409–22.
4. Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990;77:1151–63.
5. Taouli B, Ghouadni M, Corréas JM, et al. Spectrum of abdominal imaging findings in von Hippel-Lindau disease. AJR Am J Roentgenol 2003;181:1049–54.

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