Genetics Professionals Research Articles

Genetic counseling and predictive testing for hereditary neuromuscular diseases

Recent progress in genetic analysis can provide a precision diagnosis for many hereditary neuromuscular diseases in daily practice. Moreover, disease-modifying therapies such as nucleic acid medicine for patients with several neuromuscular diseases (i.e., hereditary ATTR amyloidosis, spinal muscular atrophy, and Duchenne muscular dystrophy) have been approved in Japan. For all neurologists, knowledge and practical skills of genetic counseling, especially predictive testing, will increase in importance. To promote personalized medicine for patients with neuromuscular diseases and their families, it is necessary to develop of genetic counseling systems, including nurturing genetic professionals.

Health-care practitioners’ preferences for the return of secondary findings from next-generation sequencing: a discrete choice experiment

PurposeHealth-care practitioners’ (HCPs) preferences for returning secondary findings (SFs) will influence guideline compliance, shared decision-making, and patient health outcomes. This study aimed to estimate HCPs’ preferences and willingness to support the return (WTSR) of SFs in Canada. MethodsA discrete choice experiment estimated HCPs’ preferences for the following attributes: disease risk, clinical utility, health consequences, prior experience, and patient preference. We analyzed responses with an error component mixed logit model and predicted WTSR using scenario analyses. ResultsTwo hundred fifty participants of 583 completed the questionnaire (completion rate: 42.9%). WTSR was significantly influenced by patient preference and SF outcome characteristics. HCPs’ WTSR was 78% (95% confidence interval: 74–81%) when returning SFs with available medical treatment, high penetrance, severe health consequences, and patient’s preference for return. Genetics professionals had a higher WTSR than HCPs of other types when returning SFs with clinical utility and patient preference to know. HCPs >55 years of age were more likely to return SFs compared with younger HCPs. ConclusionThis study identified factors that influence WTSR of SFs and indicates that HCPs make tradeoffs between patient preference and other outcome characteristics. The results can inform clinical scenarios and models aiming to understand shared decision-making, patient and family opportunity to benefit, and cost-effectiveness.

Experiences with offering pro bono medical genetics services in the West Indies: Benefits to patients, physicians, and the community.

We describe our experiences with organizing pro bono medical genetics and neurology outreach programs on several different resource-limited islands in the West Indies. Due to geographic isolation, small population sizes, and socioeconomic disparities, most Caribbean islands lack medical services for managing, diagnosing, and counseling individuals with genetic disorders. From 2015 to 2019, we organized 2-3 clinics per year on various islands in the Caribbean. We also organized a week-long clinic to provide evaluations for children suspected of having autism spectrum disorder. Consultations for over 100 different individuals with suspected genetic disorders were performed in clinics or during home visits following referral by locally registered physicians. When possible, follow-up visits were attempted. When available and appropriate, clinical samples were shipped to collaborating laboratories for molecular analysis. Laboratory tests included karyotyping, cytogenomic microarray analysis, exome sequencing, triplet repeat expansion testing, blood amino acid level determination, biochemical assaying, and metabolomic profiling. We believe that significant contributions to healthcare by genetics professionals can be made even if availability is limited. Visiting geneticists may help by providing continuing medical education seminars. Clinical teaching rounds help to inform local physicians regarding the management of genetic disorders with the aim of generating awareness of genetic conditions. Even when only periodically available, a visiting geneticist may benefit affected individuals, their families, their local physicians, and the community at large.

Abstract PO-050: Reducing disparities in genomic medicine using a literacy-focused genetic counseling model for cancer risk assessment

Abstract Genetic and genomic testing is reaching more people than ever, yet disparities in access to and application of hereditary cancer screening remain. Further, with the advent of lower cost sequencing, the amount and complexity of information that is conveyed to patients, including secondary results, has increased. As part of the Clinical Sequencing Evidence-Generating Research (CSER) consortium, the Cancer Health Assessments Reaching Many (CHARM) study implemented a hereditary cancer risk assessment program for healthy adults aged 18-49. Participants were recruited in English and Spanish from two primary care settings (Kaiser Permanente Northwest and Denver Health). Participants underwent clinical exome sequencing and were randomized to receive their test results via usual care or a “literacy-focused” genetic counseling approach (n=845). Genetic counselors in the literacy- focused arm received in-depth training to adapt and apply evidence-based methods for effective communication with individuals of all literacy levels. We hypothesized that the literacy-focused approach would be non-inferior to usual care genetic counseling and generate higher satisfaction, engagement, and understanding of and adherence to recommended care. We also collected qualitative data to explore the experience of receiving exome sequencing results in this setting. Here, we present findings from qualitative interviews with participants conducted within a month (n=35) and again at 6 months (n=15) after receiving results, including: pathogenic cancer risk variants, medically actionable secondary findings and carrier results; variants of uncertain significant (VUS) in cancer genes; and negative results. The mean age of participants was 33. 72% spoke English and 75% were considered medically underserved by CHARM criteria. Participants in both trial arms expressed overall satisfaction; however, some participants in the literacy-focused arm indicated that specific elements of the approach, such as teach-back and plain language, helped facilitate their understanding, while some in the usual care arm said the information was overly technical. Younger participants in both arms, whose sequencing results will not be clinically actionable for many years, reported less worry and recalled fewer details about their results than older participants. While participants recognized the utility of positive results for family, at six months only some had spoken with them about testing, and few relatives had undergone cascade testing offered by CHARM. Genomic medicine requires clear communication of disease risk and prevention recommendations. Our qualitative findings suggest that the literacy-focused approach to genetic counseling can help facilitate patient understanding of cancer and other genomic risk. These results can guide effective disclosure of sequencing results and have implications for training clinical genetics professionals in the provision of equitable care for diverse patients. Citation Format: Leslie Riddle, Laura M. Amendola, Marian J. Gilmore, Brad Rolf, Jamilyn Zepp, Claudia Guerra, Barbara Biesecker, Mikaella Caruncho, Katherine P. Anderson, Alan F. Rope, Tia L. Kauffman, Hannah Lewis, Stephanie A. Kraft, Devan M. Duenas, Benjamin Wilfond, Katrina A.B. Goddard, Galen Joseph. Reducing disparities in genomic medicine using a literacy-focused genetic counseling model for cancer risk assessment [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-050.

Parental attitudes regarding the need for genetic services in a pediatric brain tumor survivorship program

Pediatric brain tumor survivorship populations have not been typically offered genetic services as part of routine care. Genetic services can be defined as family history collection, genetic risk assessment for a patient and family members, and coordination of genetic testing. Prior research has focused on the integration of genetic services in the general pediatric oncology survivorship population and found a need for these services to be implemented. Gathering a family history and providing a genetic risk assessment have previously been determined to be an integral step in determining if an individual's cancer was due to a hereditary predisposition. The purpose of this study was to examine parental attitudes regarding the need for genetic services in their child's pediatric brain tumor survivorship clinic. Twelve semi-structured interviews were conducted with parents participating in the Brain STAR (Survivors Taking Action and Responsibility) program at Ann and Robert H. Lurie Children's Hospital of Chicago. A grounded theory approach was used to code and analyze the results thematically. Five key themes were identified: participants' perceived benefits and barriers regarding receiving genetic services, desirable time for implementation of these services, relevance of family history, and their thoughts regarding reproductive risk. These results provide insight for genetics professionals regarding the need for genetic services in this population, and how to best implement them.

Pitfalls in variant annotation for hereditary cancer diagnostics: The example of Illumina® VariantStudio®

Next Generation Sequencing (NGS), and specifically targeted panel sequencing is the state-of-the-art in clinical genetic diagnosis of Mendelian diseases. However, the bioinformatics analysis and interpretation of the generated data can be challenging. A spotlight on the default transcript selection of a user-friendly, commercially available software that is widely used by genetics professionals, i.e. Illumina® VariantStudio®, is presented. For the sake of comparison, we employed Ensembl VEP, an open-source command-line tool, as it provides flexibility regarding transcript selection. The analysis of NGS data deriving from sequencing of 857 germline DNA samples of cancer patients indicated a concordance of 82.82% between the two software programs. Significantly, using the default transcript configuration of VariantStudio®, we failed to annotate correctly 11.45% of the identified loss-of-function variants. Our results underline the importance of cautious software and transcript selection and the need for reliable, white-box data analysis, along with bioinformatics expertise in clinical diagnostics.

“It’s something I’ve committed to longer term”: The impact of an immersion program for physicians on adoption of genomic medicine

ObjectiveTo foster implementation of genomic testing in medical care by providing a cadre of physicians with ‘hands on’ experience in genomics, positioning them as opinion leaders in their medical speciality. This paper presents qualitative evaluation of immediate outcomes, in particular its impact on peer interactions. MethodsProgram design and delivery was informed by implementation science, behavior change and experiential learning theories.Inductive content analysis of transcribed audio-recordings from semi-structured post-project interviews with all participants (n = 12) was conducted. ResultsParticipants reported the immersion experience improved their genomic capability, established them as credible genomic experts within their speciality and altered their practice in genomic medicine. Participants reported strengthening and widening of peer-to-peer and interdisciplinary communication, with both passive diffusion and active dissemination of information to peers. Some also became a resource for genetic professionals. ConclusionsGenomic immersion participants described elements which support sustained integration of an innovation, including immediate changes (e.g. use of genomic tests) and wider impacts (e.g. professional networks). Practice implicationsThis study supports a role for immersion as a successful strategy for enhancing engagement of non-geneticist physicians in genomics. Additional study is needed to understand how immersion experiences change the delivery of genomic services at the provider, practice and health system level.

Old Challenges or New Issues? Genetic Health Professionals’ Experiences Obtaining Informed Consent in Diagnostic Genomic Sequencing

Background While integrating genomic sequencing into clinical care carries clear medical benefits, it also raises difficult ethical questions. Compared to traditional sequencing technologies, genomic sequencing and analysis is more likely to identify unsolicited findings (UF) and variants that cannot be classified as benign or disease-causing (variants of uncertain significance; VUS). UF and VUS pose new challenges for genetic health professionals (GHPs) who are obtaining informed consent for genomic sequencing from patients. Methods We conducted semi-structured interviews with 31 GHPs across Europe, Australia and Canada to identify some of these challenges. Results Our results show that GHPs find it difficult to prepare patients to receive results because a vast amount of information is required to fully inform patients about VUS and UF. GHPs also struggle to engage patients – many of whom may be focused on ending their ‘diagnostic odyssey’ – in the informed consent process in a meaningful way. Thus, some questioned how ‘informed’ patients actually are when they agree to undergo clinical genomic sequencing. Conclusions These findings suggest a tension remains between sufficient information provision at the risk of overwhelming the patient and imparting less information at the risk of uninformed decision-making. We suggest that a shift away from ‘fully informed consent’ toward an approach aimed at realizing, as far as possible, the underlying goals that informed consent is meant to promote.

The management of BRCA1 and BRCA2 carriers in Singapore.

Singapore is a densely populated small island nation, with a multiethnic and multireligious population. Cancer is the leading cause of death in Singapore. The population is well educated and coupled with greater awareness, there is an increasing demand for genetic testing for hereditary cancer syndromes. In Singapore, the Singapore Cancer Action Network (SCAN) guidelines for referral for genetic testing serves as a guide for clinicians on appropriate referral. We examined the important factors in genetic counselling in such a diverse population, such as acknowledgement of psychosocial impact of BRCA1/2, cultural sensitivity and upskilling of healthcare professionals. Access to genetic services in Singapore is widely available, though the number of patients who undergo testing is lower due to need for out-of-pocket costs and lack of funding from government agencies and insurance companies. The delivery of clinical care and research accrual is performed concurrently in our centre. All patients undergo pre-test counselling before giving informed consent for germline genetic testing and post-test counselling for interpretation of test results. Patients who test positive for BRCA1/2 continue to be on follow up with the cancer genetics clinic for risk-management. Predictive testing is discussed and facilitated for all at-risk relatives. Challenges faced by cancer genetics professionals in Singapore include the high rate of variant of uncertain significance (VUS) and low predictive testing rates. We hold regular support group activities for patients to seek mutual support and to raise overall awareness of BRCA1/2. We believe our comprehensive cancer genetics service serves as a useful model for other Asian countries looking to set up their own unit. We continue to aspire to empower patients, family members and healthcare professionals with cancer genetics knowledge to improve personal and public health.

Developing a core set of indicators for quality assessment of cancer genetic services

Abstract Background One of the major challenges of personalized medicine is how to assess the quality of genetic services offered both in public and private sectors. Although the quality of genetic services can be assessed and compared with structure, process or outcome measures, a consensus on the appropriate quality assessment measures is lacking worldwide. The aim of the study is to develop a core set of indicators for the quality assessment of genetic services providing testing for breast and ovarian cancer (BRCA1/2 testing). Methods In the first phase, a literature review was performed to identify genetic services providing BRCA1/2 genetic testing in Europe. In the second phase, structural, process and outcome measures retrieved from the literature records will be rated, with a 5-point Likert grading scale, by members of multinational genetic associations in a three-round Delphi survey. The survey will also accommodate quality assessment measures proposed by the participants. In the last phase, the feasibility of using a core set of indicators will be assessed across European countries. Results The literature search yielded 92 relevant records published 2000-2019, in English or Italian. The records reported outcome measures (92/92) and, to a lesser extent, process (80/92) and structure measures (71/92). An ad hoc data extraction form has been developed and the evaluation of the literature records is ongoing. Highly rated measures obtained through consensus among genetics professionals will form the core set of indicators for quality assessment of genetic services providing BRCA1/2 genetic testing. Conclusions The development of a standardized set of indicators for the assessment of genetics services is an essential step forward in defining common quality standards of the services in Europe. It will also facilitate direct comparisons across countries, highlighting examples of good practices and points of improvement for currently implemented genetic services. Key messages A minimum set of indicators for the assessment of genetics services is required to guarantee quality standards of the services across European countries. A core set of indicators will facilitate direct comparisons across European countries, underlining good practices and points of improvement for currently implemented genetic services.

Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities.

The advent of germline testing as a standard-of-care practice for certain tumor types and patients presents unique opportunities and challenges for the field of precision oncology. This article describes strategies to address workforce capacity, organizational structure, and genetics education needs within the US Department of Veterans Affairs (VA) with the expectation that these approaches may be applicable to other health care systems. Germline information can have health, reproductive, and psychosocial implications for veterans and their family members, which can pose challenges when delivering germline information in the setting of cancer care. Additional challenges include the complexity inherent in the interpretation of germline information, the national shortage of genetics professionals, limited awareness and knowledge about genetic principles among many clinicians, and organizational barriers, such as the inability to order genetic tests and receive results in the electronic health record. These challenges demand thoughtful implementation planning at the health care system level to develop sustainable strategies for the delivery of high-quality genetic services in precision oncology practice. The VA is uniquely positioned to address the integration of germline genetic testing into precision oncology practice due to its outsized role in treating veterans with cancer, training the health care workforce, and developing, testing, and implementing innovative models of clinical care.

Genetics experience impacts attitudes towards germline gene editing: a survey of over 1500 members of the public.

CRISPR-Cas9 has revolutionised genome engineering and has the potential to radically change our approach to genetic disease. However, the potential for genetic modification of embryos has raised significant and complex ethical and social concerns. The scientific community have called for ongoing stakeholder consultation about Germline Gene Editing (GGE), in particular lay publics, to help guide policy, education, research and regulatory priorities. In response, we conducted a survey to gauge public support for GGE and describe the demographic, experiential and contextual factors that influence individual attitudes. Respondent support was measured across nine hypothetical medical and enhancement GGE applications. We received responses from 1537 participants across 67 countries. Respondents were generally supportive of GGE, particularly for medical applications. While the most opposition observed was among religious respondents, those with work experience in genetics or genomics also reported greater resistance to GGE. Personal or family-related experience with genetics or genomics, identifying as female and tertiary education were also associated with less support for GGE. Further research needs to explore a diverse range of community and group attitudes towards GGE; the reasons underlying demographic and experiential differences; and to determine where the public and genetics professionals draw the line on ethical implementation respectively.

Abstract A03: Prevalence and spectrum of germline mutations in children with high-risk cancer

Abstract Introduction: Zero Childhood Cancer’s National Precision Medicine for Children with Cancer Study (PRISM) utilizes novel technologies to guide individualized management of children with high-risk cancer (expected overall survival less than 30%). Germline DNA is utilized to distinguish cancer-specific somatic variants from constitutional variants or polymorphisms, allowing identification of clinically relevant germline mutations. The prevalence of cancer predisposition syndromes in pediatric cancer may range from 8.5% to as high as 33%. Method PRISM combines molecular genomic analysis (WGS and RNASeq) with in vitro high-throughput drug screening and patient-derived xenograft drug efficacy testing. A Molecular Tumour Board (MTB) of Oncology and Genetics professionals convenes to determine the significance of genomic analysis as curated by bioinformaticians, molecular scientists, and clinicians. Results: Between September 2017 and June 2019, 218 children aged under 21 years have been recruited in PRISM (37% with central nervous system tumors, 47% with non-CNS solid tumors, and 16% with hematologic malignancies), and results are available for 208 after discussion at MTB meeting. Forty-two reportable germline variants were detected in 35 participants (detection rate: 16.8%), comprising 28 pathogenic and 14 likely pathogenic variants, across 22 cancer predisposition genes. The most frequently affected gene was CHEK2 (n=7), followed by SMARCB1 (n=5) and BRCA2 (n=3) and NF1 (3). In one out of three participants with germline mutations, somatic analysis revealed a double hit in the same gene altered in the germline. Distributions of participants with germline mutation per group were 16% of patients with CNS tumors (12/77), 19% of patients with non-CNS solid tumors (18/96), and 15% of patients with hematologic malignancies (5/34). Conclusion: Germline mutation detection rate in cancer predisposition genes was higher than expected, 16.8%; however, it may result from selection bias (i.e., cohort of high-risk cancers). Although genomic sequencing has expanded our understanding of pediatric cancer predisposition and presented opportunities for genetics-mediated care, identifying underlying germline mutations with potential clinical implications remains a clinical challenge for pediatric oncologists. Citation Format: Paulette Barahona, Alexandra Sherstyuk, Mark Cowley, Paul Ekert, Judy Kirk, Dong-Anh Khuong-Quang, Amit Kumar, Loretta Lau, Chelsea Mayoh, Glenn Marshall, Emily Moud, Tracey O’Brien, Mark Pinese, David Thomas, Vanessa Tyrell, David Ziegler, Michelle Haber, Katherine Tucker, Noemi Auxiliadora Fuentes-Bolanos, Meera Warby. Prevalence and spectrum of germline mutations in children with high-risk cancer [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A03.

Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan.

The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.

Social media usage in family communication about genetic information: 'I no longer speak with my sister but she needed to know'.

The use of social media has become a ubiquitous form of communication. Little is known about whether social media is used in families to assist with the communication of genetic information. This study aimed to understand if and why individuals use social media to communicate genetic information to at-risk relatives. Individuals with either a pathogenic variant in a cancer-predisposing gene or a heterozygous pathogenic variant in an autosomal or X-linked recessive gene were surveyed about communicating genetic information to their at-risk relatives and their use of social media to assist this process. Surveys were sent to 323 individuals from a reproductive carrier screening program and 250 individuals from a familial cancer center. The 128 responses (response rate 25.2%) showed that while most participants (79.0%) did not use social media to communicate genetic information, those that did use social media (21.0%) found it to be helpful as it was easy, accessible and allowed individuals to overcome communication barriers. Genetic professionals should be aware that social media is being used by individuals to assist family communication about genetic information and should discuss this method of communication with individuals who are faced with communicating genetic information with their family.

Adult adoptees and their use of direct-to-consumer genetic testing: Searching for family, searching for health.

Use of direct-to-consumer genetic testing (DTC-GT) is rapidly growing in the United States. Yet little is known about how specific populations like domestic and intercountry adoptees use DTC-GT. Adoptees often have little to no biological family history, which may affect how they use DTC-GT. This study aimed to examine adult adoptees' motivations to pursue DTC-GT, experiences completing a test, and reasons for not completing one. An online survey consisting of 41 closed-ended questions was distributed to domestic and intercountry adult adoptees in a snowball convenience method addressing seven areas: (a) demographics and adoption experience, (b) family health history, (c) familiarity with DTC-GT, (d) actual DTC-GT experience, (e) hypothetical DTC-GT experience, (f) health results, and (g) satisfaction with DTC-GT. Descriptive statistics were performed on participant demographics and adoption characteristics, and chi-squared and Fisher's exact tests compared demographics and adoption characteristics by familiarity with DTC-GT and completion of DTC-GT. A total of 117 adoptees met criteria and completed the survey. Adoptees were motivated to use DTC-GT to search for biological family (83.0%), verify race and ethnicity (72.3%), and find out where ancestors came from (66.0%). Most participants completed DTC-GT (80.3%); completion was significantly associated with searching for biological relatives (p<0.01) and with older age (p=0.05). For those who received health information (59.6%), 44.4% of participants reported talking with a health provider. Adoptees are using DTC-GT to search for biological relatives, confirm their ethnicity and ancestry, and gain information about their health. Genetic counselors and health professionals should be prepared to address DTC-GT with adoptees as nearly half discussed their results with providers; findings from this study provide insight into how this unique population uses DTC-GT, and the possibility of patient-centered, tailored care for adopted patients who do not have family health history.

Genetic counselors' perspectives on population-based screening for BRCA-related hereditary breast and ovarian cancer and Lynch syndrome.

Early identification of those with BRCA-related Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch syndrome has the potential for early cancer detection and/or prevention; as such, these conditions are considered Tier 1 genetic conditions by the U.S. Center for Disease Control and Prevention. Given the decreasing cost of genetic testing, population-based screening (PBS) for such conditions may be the next step toward cancer prevention. This study aimed to understand genetic counselors' perspectives toward offering PBS for the Tier 1 conditions BRCA-related HBOC and Lynch syndrome. An online survey was distributed to 3,609 members of the National Society of Genetic Counselors. A total of 367 individuals participated in the study. Fifty percent of respondents felt that PBS for inherited cancer should not be offered; 93.3% felt that the current healthcare system is unprepared for implementation of PBS. However, most respondents agreed that PBS should be implemented within the next 10years. Attitudes toward offering PBS were associated with respondents' work setting, cancer specialization, and perceived preparedness (p's<0.05). The most commonly reported barriers to the implementation of PBS were shortage of genetic professionals and lack of infrastructure. Data in this study provide evidence that infrastructural barriers and educational gaps of non-genetic professionals would need to be addressed before successful integration of PBS into the healthcare system.

Clinical Genetics Lacks Standard Definitions and Protocols for the Collection and Use of Diversity Measures

Genetics researchers and clinical professionals rely on diversity measures such as race, ethnicity, and ancestry (REA) to stratify study participants and patients for a variety of applications in research and precision medicine. However, there are no comprehensive, widely accepted standards or guidelines for collecting and using such data in clinical genetics practice. Two NIH-funded research consortia, the Clinical Genome Resource (ClinGen) and Clinical Sequencing Evidence-generating Research (CSER), have partnered to address this issue and report how REA are currently collected, conceptualized, and used. Surveying clinical genetics professionals and researchers (n = 448), we found heterogeneity in the way REA are perceived, defined, and measured, with variation in the perceived importance of REA in both clinical and research settings. The majority of respondents (>55%) felt that REA are at least somewhat important for clinical variant interpretation, ordering genetic tests, and communicating results to patients. However, there was no consensus on the relevance of REA, including how each of these measures should be used in different scenarios and what information they can convey in the context of human genetics. A lack of common definitions and applications of REA across the precision medicine pipeline may contribute to inconsistencies in data collection, missing or inaccurate classifications, and misleading or inconclusive results. Thus, our findings support the need for standardization and harmonization of REA data collection and use in clinical genetics and precision health research.

Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children.

In 2020, the Human Genetics Society of Australasia released its Position Statement on Predictive and Presymptomatic Genetic Testing in Adults and Children. This Position Statement synthesizes the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity and adults living with reduced or fluctuating capacity. Recommendations include that predictive testing in adults, young people and children should only be offered with pretest genetic counseling and the option of posttest genetic counseling. An individual considering (for themselves or on behalf of another) whether to have a predictive test should also be supported to allow them to make an autonomous and informed decision. Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies or other medical interventions in the immediate future. Where symptoms are likely to develop in childhood, in the absence of options to implement surveillance or risk reduction measures, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make their own autonomous and informed decision.

The development and evaluation of a nationwide training program for oncology health professionals in the provision of genetic testing for ovarian cancer patients

BackgroundBRCA1/2 mutation status has increasing relevance for ovarian cancer treatments, making traditional coordination of genetic testing by genetic services unsustainable. Consequently alternative models of genetic testing have been developed to improve testing at the initial diagnosis for all eligible women. MethodsA training module to enable mainstreamed genetic testing by oncology healthcare professionals was developed by genetic health professionals. Oncology healthcare professionals completed questionnaires before and 12 months post-training to assess perceived skills, competence and barriers to their coordinating genetic testing for women with high-grade non-mucinous epithelial ovarian cancer. Genetic health professionals were surveyed 12 months post-training to assess perceived barriers to implementation of mainstreaming. Results185 oncology healthcare professionals were trained in 42 workshops at 35 Australasian hospitals. Of the 273 tests ordered by oncology healthcare professionals post-training, 241 (93.1%) met national testing guidelines. The number of tests ordered by genetic health professionals reduced significantly (z = 45.0, p = 0.008). Oncology healthcare professionals' perceived barriers to mainstreamed testing decreased from baseline to follow-up (t = 2.39, p = 0.023), particularly perceived skills, knowledge and attitudes. However, only 58% reported either ‘always’ or ‘nearly always’ having ordered BRCA testing for eligible patients at 12 months, suggesting oncology healthcare professionals' perceived barriers were not systematically addressed through training. ConclusionsOncology healthcare professionals have demonstrated a willingness to be involved in the provision of genetic testing in a mainstreaming model. If oncology services are to hold responsibility for coordinating genetic testing, their readiness will require understanding of barriers not addressed by training alone to inform future intervention design.