@article {1861, title = {Molecular Characterization of a Rare Case of Bilateral Vitreoretinal T Cell Lymphoma through Vitreous Liquid Biopsy.}, journal = {Int J Mol Sci}, volume = {22}, year = {2021}, month = {2021 Jun 05}, abstract = {

Vitreoretinal lymphoma (VRL) is an uncommon eye malignancy, and VRLs of T cell origin are rare. They are difficult to treat, and their molecular underpinnings, including actionable genomic alterations, remain to be elucidated. At present, vitreous fluid liquid biopsies represent a valuable VRL sample for molecular analysis to study VRLs. In this study, we report the molecular diagnostic workup of a rare case of bilateral T cell VRL and characterize its genomic landscape, including identification of potentially targetable alterations. Using next-generation sequencing of vitreous-derived DNA with a pan-cancer 126-gene panel, we found a copy number gain of and copy number loss of tumor suppressor . To the best of our knowledge, this represents the first exploration of the T cell VRL cancer genome and supports vitreous liquid biopsy as a suitable approach for precision oncology treatments.

}, keywords = {Biomarkers, Tumor, DNA (Cytosine-5-)-Methyltransferases, DNA Copy Number Variations, DNA Methyltransferase 3A, Gene Expression Regulation, Neoplastic, High-Throughput Nucleotide Sequencing, Humans, Liquid Biopsy, Lymphoma, T-Cell, Male, Middle Aged, Neoplasm Proteins, Proto-Oncogene Proteins B-raf, Retinal Neoplasms, Vitreous Body}, issn = {1422-0067}, doi = {10.3390/ijms22116099}, author = {Cani, Andi K and Toral, Marcus A and Balikov, Daniel A and Betz, Bryan L and Hu, Kevin and Liu, Chia-Jen and Prifti, Matthew V and Chinnaiyan, Arul M and Tomlins, Scott A and Mahajan, Vinit B and Rao, Rajesh C} } @article {663, title = {Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses.}, journal = {Invest Ophthalmol Vis Sci}, volume = {57}, year = {2016}, month = {2016 05 01}, pages = {2509-21}, abstract = {

PURPOSE: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments.

METHODS: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions.

RESULTS: Most CAPN5 genetic variation occurs outside its protease core; and searches of cancer and epilepsy/autism genetic databases found no variants similar to hyperactivating retinal disease alleles. The mouse retina expressed one transcript for CAPN5 plus those of nine other calpains, similar to the human retina. In Y79 retinoblastoma cells, the level of CAPN5 transcript was very low. Immunohistochemistry detected CAPN5 expression in the inner and outer nuclear layers and at synapses in the outer plexiform layer. Western analysis of fractionated retinal extracts confirmed CAPN5 synapse localization. Western blots of fractionated brain neuronal extracts revealed distinct subcellular patterns and the potential presence of autoproteolytic CAPN5 domains.

CONCLUSIONS: CAPN5 is moderately expressed in the retina and, despite higher expression in other tissues, hyperactive disease mutants of CAPN5 only manifest as eye disease. At the cellular level, CAPN5 is expressed in several different functional compartments. CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles.

}, keywords = {Animals, Blotting, Western, Calpain, Cattle, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Male, Mice, Neoplasms, Experimental, Photoreceptor Cells, Retina, Retinal Neoplasms, Retinoblastoma, RNA, Neoplasm, Synapses, Tumor Cells, Cultured}, issn = {1552-5783}, doi = {10.1167/iovs.15-18680}, author = {Schaefer, Kellie A and Toral, Marcus A and Velez, Gabriel and Cox, Allison J and Baker, Sheila A and Borcherding, Nicholas C and Colgan, Diana F and Bondada, Vimala and Mashburn, Charles B and Yu, Chen-Guang and Geddes, James W and Tsang, Stephen H and Bassuk, Alexander G and Mahajan, Vinit B} } @article {775, title = {Infrared imaging and optical coherence tomography reveal early-stage astrocytic hamartomas not detectable by fundoscopy.}, journal = {Am J Ophthalmol}, volume = {153}, year = {2012}, month = {2012 May}, pages = {883-889.e2}, abstract = {

PURPOSE: To describe and correlate the features of astrocytic hamartomas using multimodal imaging.

DESIGN: Prospective, noncomparative, observational case series.

METHODS: This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared.

RESULTS: In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots.

CONCLUSIONS: Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.

}, keywords = {Adolescent, Astrocytes, Child, Diagnostic Imaging, Female, Fluorescein Angiography, Humans, Infrared Rays, Male, Ophthalmoscopes, Prospective Studies, Retinal Neoplasms, Tomography, Optical Coherence, Tuberous Sclerosis}, issn = {1879-1891}, doi = {10.1016/j.ajo.2011.10.033}, author = {Xu, Luna and Burke, Tomas R and Greenberg, Jonathan P and Mahajan, Vinit B and Tsang, Stephen H} }