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Next generation sequencing of vitreoretinal lymphomas from small-volume intraocular liquid biopsies: new routes to targeted therapies

Overview of attention for article published in Oncotarget, December 2016
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Mentioned by

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4 tweeters
patent
1 patent

Citations

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41 Dimensions

Readers on

mendeley
46 Mendeley
Title
Next generation sequencing of vitreoretinal lymphomas from small-volume intraocular liquid biopsies: new routes to targeted therapies
Published in
Oncotarget, December 2016
DOI 10.18632/oncotarget.14008
Pubmed ID
Authors

Andi K. Cani, Daniel H. Hovelson, Hakan Demirci, Mark W. Johnson, Scott A. Tomlins, Rajesh C. Rao

Abstract

Vitreoretinal lymphoma (VRL), the most common lymphoma of the eye, is a rare form of primary CNS lymphoma (PCNSL). Most frequently a high-grade diffuse large B cell lymphoma, VRL can cause vision loss and its prognosis remains dismal: the overall survival time is 3 years after diagnosis. Radiotherapy and chemotherapy are used but remain frequently ineffective, and no standardized treatment regimen exists. Furthermore, no biologically targeted treatments, based on the genetic profile of the tumor, are available, as VRL has hitherto not comprehensively been profiled. To address these unmet needs, we hypothesized that a next generation sequencing (NGS)-based, National Cancer Institute (NCI) MATCH Trial-modified panel would be able to identify actionable genomic alterations from small-volume, intraocular liquid biopsies. In this retrospective study, we collected diluted vitreous biopsies from 4 patients with a high suspicion for VRL. Following cytological confirmation of lymphoma (all were diffuse large B cell lymphomas), we subjected genomic DNA from the biopsies to NGS, using a panel containing 126 genes (3,435 amplicons across several hotspots per gene), which was modified from that of the NCI MATCH Trial, a new trial that has matched patients with cancers that have not responded (or never responded), to investigational therapeutics based on their prioritized mutation profile rather than site of tumor origin. Using a validated bioinformatics pipeline, we assessed for the presence of actionable mutations and copy number alterations. In all four small-volume, intraocular liquid biopsies, we obtained sufficient genomic DNA for analysis, even in diluted samples in which the undiluted vitreous was used for cytology and flow cytometry. Using NGS, we found targetable heterozygous gain-of-function mutations in the MYD88 oncogene, and confirmed in our cohort the presence the L265 mutations, previously described using PCR-based assays. For the first time in VRL, we also identified the MYD88 S243N mutation. We also identified two-copy copy number losses in the tumor suppressor CDK2NA in all four cases, and one copy loss of the tumor suppressor PTEN in one sample. In one case, in which vitreous biopsies were originally read as cytologically negative, but which was confirmed as lymphoma when a lesion appeared in the brain two years later, our NGS-based approach detected tumoral DNA in the banked, original liquid biopsy. We performed the first systematic exploration of the actionable cancer genome in VRL. Our NGS-based approach identified exploitable genomic alterations such as gain-of-function MYD88 oncogene mutations and loss of the tumor suppressor CDK2NA, and thus illuminates new routes to biologically targeted therapies for VRL, a cancer with a dismal prognosis. This precision medicine strategy could be used to nominate novel, targeted therapies in lymphomas and other blinding and deadly ocular, orbital, and ocular adnexal diseases for which few treatments exist.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Denmark 1 2%
Unknown 45 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 22%
Researcher 6 13%
Student > Bachelor 5 11%
Student > Master 4 9%
Other 4 9%
Other 8 17%
Unknown 9 20%
Readers by discipline Count As %
Medicine and Dentistry 16 35%
Biochemistry, Genetics and Molecular Biology 11 24%
Computer Science 3 7%
Engineering 2 4%
Neuroscience 2 4%
Other 3 7%
Unknown 9 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 July 2020.
All research outputs
#4,509,966
of 16,884,169 outputs
Outputs from Oncotarget
#1,678
of 13,257 outputs
Outputs of similar age
#113,001
of 392,437 outputs
Outputs of similar age from Oncotarget
#135
of 709 outputs
Altmetric has tracked 16,884,169 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 13,257 research outputs from this source. They receive a mean Attention Score of 4.4. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 392,437 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 709 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.