POT1 and multiple primary melanomas: the dermatological phenotype.

POT1 is the second most frequently reported gene (after CDKN2A) in familial melanoma. Pathogenic variants are associated with earlier onset and/or multiple primary melanomas (MPMs). To date, POT1 phenotypical reports have been largely restricted to associated malignancies, and description of the dermatological landscape has been limited. We identified 10 variants in n=18 of 384 (4.7%) unrelated individuals (n=13 MPMs; n=5 single primary melanomas) of European ancestry. Five variants were rare (minor allele frequency <0.001) or novel (two loss-of-function (LOF), one splice acceptor and two missense) and were predicted to be functionally significant, in five unrelated probands with MPMs (≥3 melanomas). We performed three-dimensional total body photography on both individuals with confirmed pathogenic LOF variants to characterise the dermatological phenotype. Total body naevus counts (≥2 mm diameter) were significantly higher (p=7.72×10-12) in carriers compared with a control population. Majority of naevi were on the probands' back and lower limb regions, where only mild to moderate ultraviolet (UV) damage was observed. Conversely, the head/neck region, where both probands exhibited severe UV damage, had comparably fewer naevi. We hypothesise that carriage of functionally significant POT1 variants is associated with increased naevus counts generally, and naevi >5 mm in diameter specifically and the location of these are independent of UV damage.

MITF E318K: A rare homozygous case with multiple primary melanoma.

MITF E318K moderates melanoma risk. Only five MITF E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total-body-photography (TBP) to describe the dermatological phenotype of a homozygous MITF E318K individual. The case, a 32-year-old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre-existing naevi and one was a rare naevoid melanoma. 3D-TBP revealed a high naevus count (n = 162) with pigmentation varying from light to dark. Most naevi generally (n = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (n = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the MITF E318K homozygosity, there was heterozygosity for four other moderate-risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance.

Measurable outcomes of consumer engagement in health research: A scoping review.

Background: Consumer engagement is increasingly recognized as an instrumental component of health research, with many institutions and international bodies mandating it as part of the research and funding process. Given an increasing utilization of consumer engagement in health research, it is critical to identify the literature which support its value and tools that capture successful outcomes. To develop an overview of the literature, we conducted an umbrella scoping review exploring important outcomes of consumer engagement in health research combined with a scoping review of relevant frameworks. Specifically, we aimed to capture outcomes which reflect authentic and meaningful consumer engagement. Methods: Four databases (PubMed, Embase, CINAHL and Cochrane Library) were searched using key search terms. Records were included if they were review articles or frameworks that addressed outcomes of consumer engagement in health research. Data was analyzed using descriptive statistics and an inductive qualitative content analysis. Identified outcomes were sorted based on the three most relevant stakeholder groups (consumer, researcher, institution). Results: A total of twenty articles that explored a variety of health disciplines were included. We identified fifteen measurable outcomes of consumer engagement in health research. Eight core outcomes were relevant to all stakeholder groups, and were considered fundamental to authentic consumer engagement including (1) trust, (2) empowerment, (3) respect, (4) confidence in the outcomes of the research, (5) transparency of the research process, (6) satisfaction with the consumer engagement program, (7) knowledge and experiences of consumers, and (8) degree of consumer engagement. Outcomes pertaining to specific stakeholder groups included representativeness and diversity of the consumer groups, research relevance to consumers, funding opportunities, quality/validity of the research, recruitment/retention rates, translation and dissemination of research, and interpretation of results. Conclusion: This review identified key measurable outcomes that could be captured when evaluating the impacts of consumer engagement on health research and the success of consumer engagement programs. All outcomes identified were relatively underexplored within the literature, and inadequately and/or inconsistently evaluated amongst studies. Future research should consult all stakeholder groups to identify outcomes perceived to be reflective of optimal consumer engagement.