It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer.

The aim of this review is to summate the eye involvement in patients with mucopolysaccharidoses (MPS) using current ocular imaging techniques, their advantages and disadvantages and how they may aid diagnosis, management and monitoring. We critically reviewed the current literature surrounding MPS and recent imaging technology as well as histology. Primary searches of PubMed and Web of Science were performed. We reviewed all papers on the topic published and summarized the findings of each medical device as well as the advantages and disadvantages of using these for the MPS patient. We discussed the potential of each of these devices to monitor potential ocular pathology in the MPS cohorts in the order of MPS subtype. We reviewed imaging techniques involving use of the Iris Camera, Pentacam, Optical Coherence Tomography (OCT) as well as ultrasound and Heidelberg OCT. The need for reliable objective quantification of eye findings in MPS has led to utilization of new imaging technologies described here, and future use will enhance our understanding of the unique eye features in MPS. In particular, we note that the Pentacam and iris camera are able to provide objective measurements of corneal haze and monitor ocular response to treatment.

The ocular phenotype in MPS is variable, with corneal clouding occurring in MPSI, MPSIV and MPSVI, and retinopathy in MPSI only. There was an association between corneal clouding and efficacy of systemic treatment as measured by biomarkers.

Citation: Javed A, Aslam T, Jones SA, Ashworth J. Objective quantification of changes in corneal clouding over time in patients with mucopolysaccharidosis. Invest Ophthalmol Vis Sci. 2017;58:954-958. DOI:10.1167/ iovs.16-20647 PURPOSE. We determine objective changes in corneal opacification levels over time in patients with mucopolysaccharidoses (MPS) treated with enzyme replacement therapy or hematopoietic stem cell transplant. A prospective cohort study was done of 9 patients with MPS I (Hurler) or VI (Maroteaux-Lamy).METHODS. Quantification of corneal clouding using the Iris camera and full ophthalmic examination, including subjective assessment of corneal clouding, was done in 2011 and repeated in 2015/2016. Patients also had assessment of biomarkers, including dermatan sulfate/chondroitin sulfate (DS/CS) ratio. Change in corneal opacification were measured by Iris camera corneal opacification measure (COM) score during a mean of 60 months followup. RESULTS.A total of 5/17 (29%) eyes had a deterioration in COM score, indicating increased corneal clouding. There was no significant change in COM score in 10/17 (59%) patient eyes. One patient (2/17 eyes) demonstrated significant improvement in corneal clarity and this was associated with improved biomarker levels.CONCLUSIONS. Assessment of COM scores using the Iris camera are an objective means of monitoring corneal opacification over time in patients with MPS. Corneal opacification may potentially be reversed with intensive treatment demonstrated by impact on biomarkers.Keywords: mucopolysaccharidoses, paediatric ophthalmology, metabolic medicine T he mucopolysaccharidoses (MPS) are a group of rare metabolic diseases characterized by defects of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Glycosaminoglycan deposition in multiple tissues and organs results in a wide range of systemic manifestations, including dysmorphic facial features, vision and hearing impairment, cardiorespiratory problems, joint and bone diseases, neurologic problems, and intellectual impairment. Corneal opacification is an early clinical feature in several of the MPS subtypes (MPSI Hurler and Hurler-Scheie, MPSIVA Morquio, MPSVI Maroteaux-Lamy, MPSVII Sly), and can result in significant visual impairment.1 In addition, complications, such as retinopathy, glaucoma, and optic neuropathy, may contribute to visual loss in patients with MPS. Current treatment options for MPS include enzyme replacement therapy (ERT), which is available for MPS I, II, IVA, and VI; and hematopoietic stem cell transplantation (HSCT), which is useful for selected patients with MPS types I and VI.1,2 The untreated clinical course of corneal clouding in MPS is thought to be one of gradual deterioration, but the extent and speed of deterioration have not been documented. Enzyme replacement therapy is known to be effective in improving the systemic manifestations of MPS in types I, II, IVA, and VI by improving respiratory function and stamina, and improving quality of life.2...

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Improved ocular phenotypes in MPSI are associated with markers signifying efficacy of prior transplant. Early and effective HSCT may result in a better visual prognosis and reduction in ocular complications for patients with MPSI.

BackgroundAfrican American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer.MethodsWe retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions. The 12-gene assay and mismatch repair (MMR) status were performed by Genomic Health (Redwood City, California). Student’s t-test and the Wilcoxon rank sum test were used to compare Recurrence Score data and gene expression data from AA and CA patients (SAS Enterprise Guide 5.1).ResultsSamples from 122 AA and 122 CA patients were analyzed. There were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median age was 66 years for AA patients and 68 for CA patients. Age, gender, year of surgery, pathologic T-stage, tumor location, the number of lymph nodes examined, lymphovascular invasion, and MMR status were not significantly different between groups (p = 0.93). The mean Recurrence Score result for AA patients (27.9 ± 12.8) and CA patients (28.1 ± 11.8) was not significantly different and the proportions of patients with high Recurrence Score values (≥41) were similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC and GADD45B), was significantly different between the racial groups. After controlling for clinical and pathologic covariates, the means and distributions of Recurrence Score results and gene expression profiles showed no statistically significant difference between patient groups.ConclusionThe distribution of Recurrence Score results and gene expression data was similar in a cohort of AA and CA patients with stage II colon cancer and similar clinical characteristics, suggesting that tumor biology, as represented by the 12-gene assay, did not differ between patient groups.

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