Malignant peripheral nerve sheath tumor on a patient with a maternally inherited novel NF1 gene pathogenic germline variant: Case report.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome caused by pathogenic variants in NF1, which negatively regulates the RAS pathway. Knowledge of the genotype-phenotype correlation in this disease is an important tool for prognostic evaluation and early detection of malignant peripheral nerve sheath tumors (MPNST), present in approximately 10% of these patients. We present the case of a teenager with a left jaw MPNST and a previously unreported germline pathogenic variant on NF1. CASE PRESENTATION: An 11-year-old female with a NF1 clinical diagnosis was referred to our hospital with a MPNST in an advanced state. A previously unreported NF1 pathogenic variant was obtained (GRCh37: NM_182493.2 c.3299C>G, p.Ser1100*). Despite great efforts from the surgical and medical teams, the tumor progression couldn't be halted, resulting in the patient's death. DISCUSSION: As MPNSTs are refractory to current treatment regimens, early diagnosis, and development of new therapies, such as MEK inhibitors, is necessary for reducing morbidity and mortality within NF1 patients. This increases the importance of a more widespread genetic testing strategy. CONCLUSION: The report of a novel NF1 pathogenic variant in a patient with maternally inherited neurofibromatosis type 1 and a MPNST increases the knowledge of the genotype-phenotype correlation in the disease.

Evaluating the Effectiveness of a Telehealth Cancer Genetics Program: A BRCA Pilot Study.

INTRODUCTION: Ashkenazi Jewish (AJ) individuals face a 1 in 40 (2.5%) risk of having a BRCA mutation, which is 10 times the general population risk. JScreen launched the PEACH BRCA Study, a telehealth-based platform for BRCA education and testing, with the goal of creating an effective model for BRCA testing in low-risk AJ individuals who do not meet national testing criteria. Other goals were to determine the rate of BRCA mutations in this group, to assess the adequacy of screening for the 3 common AJ founder mutations only, and to assess satisfaction with the telehealth model to help inform a national launch of a broader cancer genetic testing program. METHODS: Criteria for participation included those who were AJ, resided in the metro-Atlanta area, were aged 25 and older, and had no personal or close family history of BRCA-related cancers. Pre-test education was provided through a video and written summary, followed by complimentary BRCA1/2 sequencing and post-test genetic counseling. Participants responded to pre- and post-test surveys, which assessed knowledge and satisfaction. Those who were not eligible to participate were sent genetic counseling resources and later surveyed. RESULTS: Five hundred one participants were tested and the results included 4 positives (0.8% positivity rate), 494 negatives, and 3 variants of uncertain significance. Overall satisfaction with the study process was high (96.9/100), knowledge about BRCA was high (97.5% of participants passed a pre-test knowledge quiz), and satisfaction with pre- and post-test education was high (97.9% of participants were satisfied with the pre-test video and written summary, and 99.5% felt that their post-test genetic counseling session was valuable). Many participants expressed interest in receiving broader cancer testing. CONCLUSIONS: The BRCA founder mutation rate in a low-risk AJ population was significantly lower than the previously established AJ rate of 1 in 40. It was also determined that a telehealth model for a cancer genetics program is effective and acceptable to the population tested. This study established interest in broader cancer genetic testing through a telehealth platform and suggested that testing may be successful in the Jewish community at a national level and potentially in other populations, provided that patient education and genetic counseling are adequately incorporated.

Distress facing increased genetic risk of cancer: The role of social support and emotional suppression.

OBJECTIVES: Healthy individuals from hereditary cancer families undergoing genetic testing for cancer susceptibility (GTC) report more distress when they perceive their social support as low and suppress their emotions. This study aimed to explore how suppressing emotions and perceiving others as unsupportive are related with cancer-risk distress. METHODS: We performed a regression-based mediation analysis to assess if expressive suppression mediates or is mediated by perceived social support in the relation with cancer-risk distress. Participants were 125 healthy adults aged over 18 (M = 36.07, SD = 12.86), mostly female (72,4%), who undergone GTC to assess the presence of hereditary breast and ovarian cancer or Lynch syndromes. RESULTS: Controlling for age and gender, we found a moderate size indirect effect of social support on cancer-risk distress through expressive suppression (ß = -0.095) and a direct effect of expressive suppression on cancer-risk distress. CONCLUSIONS: When healthy individuals from hereditary cancer families perceive their social network as less responsive, they tend to not express their emotions, which relates to increased distress facing GTC. PRACTICE IMPLICATIONS: Practitioners may assess cancer-risk related distress before the GTC and offer distressed individuals interventions focused on changing emotion regulation strategies in a safe group context.

Genodermatoses - Opportunities for Early Detection and Cancer Prevention.

Purpose of Review: This review describes the clinical features of the major adult-onset genodermatosis-associated hereditary cancer predisposition syndromes. Diagnosis of these conditions can be challenging due to a wide range of clinical features, varied presentations within families and the involvement of multiple medical specialities. Recent Findings: By emphasising the cutaneous and other non-malignant features, we aim to alert clinicians from all specialities to clues in the clinical history which should prompt consideration of a genodermatosis-associated hereditary cancer predisposition syndrome. In recognition of the move towards remote (telephone or video) appointments since the Covid-19 pandemic, we propose criteria which could be used by Cancer Genetics services to triage patients for in-person consultations in order to examine for signs of genodermatosis. Summary: Although individually rare, familiarity with these conditions amongst genetic and non-genetic clinicians is important as early diagnosis provides an opportunity to implement risk-reduction measures prior to a cancer diagnosis.

Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals.

Background: The SARS-CoV-2 pandemic introduced a global distraction effect in cancer patients' care. The aim of this study was to explore the effect of the pandemic on the largest molecular diagnostics center for cancer patients and high-risk individuals in Serbia.Research design and methods: EGFR, KRAS/NRAS, BRAF, and BRCA1/2 mutation testing were performed by qPCR and NGS. NGS was used for panel testing of hereditary breast/ovarian cancer and cancers associated with Lynch syndrome. The analytical output during the state of emergency (SoE) was compared to the period before and after the outbreak using one-way ANOVA. Statistical significance was set at p < 0.05.Results: A 38% reduction in the number of analysis was detected during the SoE. After the SoE, a 19% reduction was noted compared to SoE and 50% compared to the period before the SoE (p = 0.038). Three of the 48 scheduled appointments for pretest genetic counseling were carried out during the SoE, but the number of NGS tests increased by 50%.Conclusions: The SARS-CoV-2 pandemic had a profound negative effect on the diagnostic output of our centralized molecular diagnostics center. The only positive effect was shortening of waiting lists for hereditary cancer patients and high-risk individuals.