Implementing a Virtual Health Telemedicine Program in a Community Setting.

Aurora Health Care in eastern Wisconsin has a clinical genetics program driven by genetic counselors in the cancer/adult and prenatal genetics settings. In 2015, the workforce shortage of genetic counselors left us with 4 open positions for genetic counselors that we were unable to fill. We explored many models of alternative service delivery, and determined virtual health (VH) via telemedicine to be the best option for our system. Historically, telemedicine technologies have been used to provide access to healthcare services to patients in remote areas. We, however, were struggling to find genetics counselors to staff both our remote clinics and urban clinics. To solve this problem, we recruited genetic counselors from across the country to work remotely from their current home or home office utilizing VH to staff our clinics. We then created clinical workflows and an implementation process of virtual health for 9 prenatal and cancer clinics across the eastern Wisconsin footprint of our healthcare system over the course of 12 months. Here we provide our experience and process in establishing a VH program in order to help other institutions that have been affected by the workforce shortage of clinical genetics professionals.

Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes.

Germline variants in tumor suppressor genes (TSGs) can result in RNA mis-splicing and predisposition to cancer. However, identification of variants that impact splicing remains a challenge, contributing to a substantial proportion of patients with suspected hereditary cancer syndromes remaining without a molecular diagnosis. To address this, we used capture RNA-sequencing (RNA-seq) to generate a splicing profile of 18 TSGs (APC, ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, and TP53) in 345 whole-blood samples from healthy donors. We subsequently demonstrated that this approach can detect mis-splicing by comparing splicing profiles from the control dataset to profiles generated from whole blood of individuals previously identified with pathogenic germline splicing variants in these genes. To assess the utility of our TSG splicing profile to prospectively identify pathogenic splicing variants, we performed concurrent capture DNA and RNA-seq in a cohort of 1000 patients with suspected hereditary cancer syndromes. This approach improved the diagnostic yield in this cohort, resulting in a 9.1% relative increase in the detection of pathogenic variants, demonstrating the utility of performing simultaneous DNA and RNA genetic testing in a clinical context.

Coordinating an Oncology Precision Medicine Clinic Within an Integrated Health System: Lessons Learned in Year One.

Precision medicine is a term describing strategies to promote health and prevent and treat disease based on an individual's genetic, molecular, and lifestyle characteristics. Oncology precision medicine (OPM) is a cancer treatment approach targeting cancer-specific genetic and molecular alterations. Implementation of an OPM clinical program optimally involves the support and collaboration of multiple departments, including administration, medical oncology, pathology, interventional radiology, genetics, research, and informatics. In this review, we briefly introduce the published evidence regarding OPM's potential effect on patient outcomes and discuss what we have learned over the first year of operating an OPM program within an integrated health care system (Aurora Health Care, Milwaukee, WI) comprised of multiple hospitals and clinics. We also report our experience implementing a specific OPM software platform used to embed molecular panel data into patients' electronic medical records.

Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series.

OBJECTIVE: Germline loss-of-function mutations in succinate dehydrogenase (SDHx) genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor SDHx mutations. PATIENTS AND RESULTS: We report four unrelated patients with ACC and SDHx mutations. All cases presented with Cushing syndrome and large adrenal masses that were confirmed to be ACC on pathology. All four ACC specimens were found to have truncating mutations in either SDHC or SDHA, while cases 1, 2 and 3 also had the mutations confirmed in the germline: Case 1: SDHC c.397C > T, pR133X; Case 2: SDHC c.43C > T, p.R15X; Case 3: SDHA c.91C > T, p.R31X; Case 4: SDHA c.1258C > T, p.Q420X. Notably, Case 1 had a father and daughter who both harbored the same SDHC germline mutation, and the father had a paraganglioma and renal cell carcinoma. A combination of next generation sequencing, and/or immunohistochemistry, and/or mass spectroscopy was used to determine whether there was loss of heterozygosity and/or loss of SDH protein expression or function within the ACC. Potential evidence of loss of heterozygosity was observed only in Case 2. CONCLUSIONS: We observed truncating mutations in SDHA or SDHC in the ACC and/or germline of four unrelated patients. Given how statistically improbable the concurrence of ACC and pathogenic germline SDHx mutations is expected to be, these observations raise the question whether ACC may be a rare manifestation of SDHx mutation syndromes. Further studies are needed to investigate the possible role of SDH deficiency in ACC pathogenesis.

Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound.

OBJECTIVE: This study aimed to determine if screening patients based on certain cancer syndromes or family history criteria can lead to early detection of pancreatic cancer. METHODS: This was a cohort study from 2008 to 2011 at a large tertiary referral center. A total of 30 patients met high-risk criteria after genetic counseling and were referred to a gastroenterologist for possible endoscopic ultrasound (EUS). RESULTS: Of the 30 patients, 16 underwent EUS. Subsequently, 3 patients had fine needle aspiration. Two patients had pancreatic adenocarcinoma, and 1 patient had an intraductal papillary mucinous neoplasm with low-grade dysplasia. The 2 patients with pancreatic adenocarcinoma both had breast cancer and BRCA2 mutations. The patient with the intraductal papillary mucinous neoplasm had Peutz-Jeghers syndrome. All 3 patients underwent surgery and have remained cancer free. CONCLUSIONS: Genetic risk assessment with EUS +/- fine needle aspiration in high-risk patients may lead to earlier detection of pancreatic cancer and potentially improve overall morbidity and mortality. Greater emphasis should be placed on screening patients for hereditary cancer syndromes that increase the risk of pancreatic cancer.

Assessment of clinical practices among cancer genetic counselors.

Various models of cancer genetics service delivery have been published, and practice guidelines were set forth by the National Society of Genetic Counselors (NSGC) in 2004. While the demand for services has increased, there has not been a comprehensive study of current practice models. An online survey of the NSGC Familial Cancer Risk Counseling Special Interest Group was conducted to study current methods of providing clinical cancer genetics services. Respondents were asked to quantify patient volume, support staff availability, and physician involvement in cases. Two case examples were used to further describe current practices including the number of genetic counseling tasks performed, time spent in these tasks, and number of in-person visits versus phone encounters. Although published cancer genetic counseling guidelines advise a 3-visit model (initial consult, sample draw, and result disclosure), 29.3% of respondents have adopted a 1-visit model, where the sample is drawn at the first visit and phone disclosure replaces the third visit. The content of the initial consult does not vary significantly, and is consistent with the NSGC practice guidelines. Furthermore, 56% report spending >15 min on case preparation, and 27 respondents self-reported redundancy in tasks such as documentation. It appears that a proportion of genetic counselors are following a new model of service delivery. However, insufficient documentation and case preparation are apparent, and many respondents reported lack of support staff as a barrier to efficient patient care. Factors contributing to the variability in current practice, and how they affect efficiency, require further study.