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Liquid Biopsy and Molecular Diagnosis of Ocular Lymphoma

Jun 15 2021

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20/20 Blog

Palo Alto, CA — A study by the Mahajan Lab, in close collaboration with Rajesh Rao’s lab at the University of Michigan, helps improve our understanding of vitreoretinal lymphomas (VRLs) and demonstrates how liquid vitreous biopsies can be used for precise, personalized molecular diagnoses capable of guiding effective treatments. 

Vitreoretinal lymphomas (VRLs) are potentially fatal blood cell cancers that occur inside the eye. These cancers threaten vision, but they can also be a sign of cancer elsewhere in the body, including the central nervous system. 

Vitreoretinal lymphoma cancer is rare, representing only 4-6% of all brain tumors and <1% of all non-Hodgkin’s lymphomas, so only a handful of cases are identified each year.  

Patients affected by VRL are at risk of delayed diagnosis and treatment due to a lack of clinical approaches with high diagnostic accuracy and an incomplete understanding of VRL pathophysiology. 

Vinit Mahajan M.D.,Ph.D, Stanford associate professor and vice chair of ophthalmology  reseaerch, said, “By looking at the genetic makeup of VRLs and other rare diseases, we are opening up new pathways for the diagnosis and treatment of diseases that have eluded us. Our Stanford ophthalmology biorepository stores eye tissues that could hold the key to a goldmine of new medical breakthroughs.” 

The study, published in the International Journal of Molecular Sciences, describes analysis of rare liquid vitreous biopsies obtained from the eyes of a patient suspected of VRL. 

Using next generation DNA sequencing technology, the collaborating research teams identified a rare clonal T-cell population within the vitreous biopsy.

Marcus Toral, an M.D., Ph.D. student in Mahajan’s lab explained, “We were able to precisely characterize the DNA fingerprint within these T-cells. We found increased copies of the BRAF cancer gene along with reduced copies of the tumor suppressor gene, DNMT3A.” 

This work is the first analysis of an ocular T-cell lymphoma genome. The study demonstrates how liquid vitreous biopsies coupled with next generation DNA sequencing technologies can be used to improve VRL diagnosis. Knowing the specific cancer gene mutations can guide physicians in selecting specific cancer drugs. 

Mahajan said, “This precision medicine approach can be used with other eye cancers, giving physicians and patients hope for more personalized treatments and potential cures.

The manuscript, “Molecular characterization of a rare case of bilateral vitreoretinal Tcell lymphoma through vitreous liquid biopsy,” was published in International Journal of Molecular Science.

Co-authors include: Andi K Cani, Marcus A Toral, Daniel A Balikov, Bryan Betz, Kevin Hu, Chia-Jen Liu, Matthew L Prifti, Arul M Chinnaiyan, Scott A Tomlins, Vinit B
Mahajan *, Rajesh C Rao *( co-corresponding authors).