Duplex Ratio Tests as Diagnostic Biomarkers in Malignant Melanoma.

Chromosomal instability is a well-described feature of malignant tumors. Melanomas have typical patterns of chromosomal instability compared with benign nevi, which have minimal DNA copy number change. A few malignant melanomas and their benign counterparts, nevi, prove difficult to diagnose on histopathologic analysis alone, which is currently the gold standard. Quantitative PCR-based assays called duplex ratio tests (DRTs) have been developed by our laboratory for application using DNA from FFPE samples of melanomas and nevi. The reproducibility and accuracy of the DRTs were demonstrated and appropriate correction factors for DNA quality calculated for each assay, based on the results of 108 diploid samples. As a panel, seven DRTs were able to differentiate unambiguous cases of melanoma and nevi with a sensitivity of 87% (95% CI, 83%-91%) and a specificity of 88% (95% CI, 84%-92%) in a series of 145 melanomas and 123 nevi. The DRT scores for 20 nonmetastasizing primary melanomas and 20 metastasizing primary melanomas revealed that DRTs had a marginal benefit as prognostic markers. DRTs have early potential to act as molecular biomarkers of melanoma on FFPE specimens pending validation, and DRTs may have applicability as prognostic markers in melanoma or other tumor types if new DRTs to relevant loci are developed.

The accrual of bone mass during childhood and puberty.

PURPOSE OF REVIEW: To assess factors that influence the tempo of bone mass accrual with emphasis on obesity, exercise, and nutritional factors. RECENT FINDINGS: The prevalence of childhood obesity has increased dramatically throughout the world. Recent studies suggest that adiposity may be detrimental to development of bone strength parameters, and bone mass accrual during growth. Weight-bearing exercise during prepubertal and peripubertal period appears to enhance bone strength parameters. Maternal ultraviolet B radiation exposure and vitamin D status has been shown to have a positive effect on neonatal bone status, which appears to track up to the prepubertal period. Administration of vitamin D with or without calcium, but not calcium alone, during the prepubertal period might be an important 'window' for improving skeletal mineralization. SUMMARY: Obesity in children appears to be detrimental to development of bone strength parameters and bone mass accrual. Weight-bearing exercise during prepubertal and peripubertal period and vitamin D supplementation during pregnancy, infancy, and peripubertal period might be important for bone mass accrual. However, adequately powered randomized controlled trials with follow-up into adulthood are needed to determine if these interventions improve the tempo of bone mass accrual.