A germline polymorphism of the microphthalmia transcription factor (MITF) gene encoding a SUMOylation-deficient E318K-mutated protein has recently been described as a medium-penetrance melanoma gene. In a clinical assessment of nevi from 301 volunteers taken from Queensland, we identified six individuals as MITF E318K mutation carriers. The phenotype for 5 of these individuals showed a commonality of fair skin, body freckling that varied over a wide range, and total nevus count between 46 and 430; in addition, all were multiple primary melanoma patients. The predominant dermoscopic signature pattern of nevi was reticular, and the frequency of globular nevi in carriers varied, which does not suggest that the MITF E318K mutation acts to force the continuous growth of nevi. Excised melanocytic lesions were available for four MITF E318K carrier patients and were compared with a matched range of wild-type (WT) melanocytic lesions. The MITF staining pattern showed a predominant nuclear signal in all sections, with no significant difference in the nuclear/cytoplasmic ratio between mutation-positive or -negative samples. A high incidence of amelanotic melanomas was found within the group, with three of the five melanomas from one patient suggesting a genetic interaction between the MITF E318K allele and an MC1R homozygous red hair color (RHC) variant genotype.

Purpose This study examined the accuracy and potential clinical utility of two expedited transcription methods for narrative language samples elicited from school-age children (7;5–11;10 [years;months]) with developmental language disorder. Transcription methods included real-time transcription produced by speech-language pathologists (SLPs) and trained transcribers (TTs) as well as Google Cloud Speech automatic speech recognition. Method The accuracy of each transcription method was evaluated against a gold-standard reference corpus. Clinical utility was examined by determining the reliability of scores calculated from the transcripts produced by each method on several language sample analysis (LSA) measures. Participants included seven certified SLPs and seven TTs. Each participant was asked to produce a set of six transcripts in real time, out of a total 42 language samples. The same 42 samples were transcribed using Google Cloud Speech. Transcription accuracy was evaluated through word error rate. Reliability of LSA scores was determined using correlation analysis. Results Results indicated that Google Cloud Speech was significantly more accurate than real-time transcription in transcribing narrative samples and was not impacted by speech rate of the narrator. In contrast, SLP and TT transcription accuracy decreased as a function of increasing speech rate. LSA metrics generated from Google Cloud Speech transcripts were also more reliably calculated. Conclusions Automatic speech recognition showed greater accuracy and clinical utility as an expedited transcription method than real-time transcription. Though there is room for improvement in the accuracy of speech recognition for the purpose of clinical transcription, it produced highly reliable scores on several commonly used LSA metrics. Supplemental Material https://doi.org/10.23641/asha.15167355

Malignant melanomas often arise from nevi, which result from initial oncogene-induced hyperproliferation of melanocytes that are maintained in a CDKN2A/p16-mediated senescent state. Thus, genes that can bypass this senescence barrier are likely to contribute to melanoma development. We have performed a gain-of-function screen of 17,030 lentivirally expressed human open reading frames (ORFs) in a melanoma cell line containing an inducible p16 construct to identify such genes. Genes known to bypass p16-induced senescence arrest, including the human papilloma virus 18 E7 gene ( HPV18E7), and genes such as the p16-binding CDK6 with expected functions, as well as panel of novel genes, were identified, including high-mobility group box (HMGB) proteins. A number of these were further validated in two other models of p16-induced senescence. Tissue immunohistochemistry demonstrated higher levels of CDK6 in primary melanomas compared with normal skin and nevi. Reduction of CDK6 levels drove melanoma cells expressing functional p16 into senescence, demonstrating its contribution to bypass senescence.