BackgroundIntratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS) of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood.MethodsWhole genome NGS was performed on 12 µg (range 11.1–13.3 µg) of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis.ResultsWhole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome.ConclusionThis case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples.
PurposeWe report an update on a recently published case of uncontrolled hypertension secondary to immunoglobulin A (IgA) nephropathy resulting in massive bilateral retinal and choroidal infarction.ObservationsIn our previous report, we presented a 30-year old female with end-stage renal disease who complained of painless vision loss after many missed hemodialysis. The patient was found to be in hypertensive crisis resulting in massive retinal and choroidal infarction with severe vision loss in both eyes. The patient was treated with pan-retinal photocoagulation (PRP) with intravitreal Bevacizumab and was subsequently lost to follow-up. In this update, we report the complications that followed. After many months, she presented to clinic with a blind painful right eye. She was found to have a further decrease in vision with neovascular glaucoma in the right eye and a tractional retinal detachment in the left eye. The patient ultimately elected for enucleation of her right eye. Immunohistopathology revealed IgA deposition, confirming the presumed diagnosis of IgA nephropathy, previously unconfirmable through renal biopsy.Conclusions and ImportanceThere is a strong association between severity of retinopathy and level of kidney function. Although a rare presentation, hypertensive retinopathy is a common complication of end-stage renal disease and can be a devastating process as emphasized by this report. Those with auto-immune renal disease, such as IgA nephropathy, are at higher risk for retino-choroidal complications. It should remind all ophthalmologists and clinicians on the necessity of closer eye examinations for these patients, particularly for those with auto-immune renal disease.
BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the difference between widefield confocal scanning laser imaging (WSLO) and widefield broad line fundus (WBLF) imaging in their ability to view the peripheral retina in routine clinical practice. PATIENTS AND METHODS: A retrospective chart review identified patients within routine clinical practice who were imaged with a WSLO image and a single and montaged WBLF image. The primary outcome was the number of ultra-widefield quadrants captured utilizing the UWF consensus definitions. Secondary outcomes included the area within each of quadrant and the differences in clinical grading between modalities. RESULTS: More vortex ampullae were identified with the WSLO than either single image or montage WBLF image. The WSLO captured 116 of the possible 260 vortex ampullae (45%) in comparison to the WBLF single image (8 of 260; 3%) and WBLF montage (96 of 260; 37%). Only five eyes from WSLO and no images from the WBLF single image met the ultra-widefield consensus definition in routine clinical practice. The average area per individual quadrant acquired by WSLO image was greater than the single or montage WBLF image (781.67 mm 2 , 433.82 mm 2 , and 686.03 mm 2 , respectively; P < .001). Clinical grading of images found a substantial inter-rater agreement with both technologies (86% on WSLO; 88% on WBLF). CONCLUSIONS: Both systems had a low rate of meeting UWF consensus definitions in routine clinical practice. A single WSLO image acquired a greater area than WBLF image in both single-image and montage formats. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:89–94.]
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