The Ophthalmic Experience: Unanticipated Primary Findings in the Era of Next Generation Sequencing

Next generation sequencing (NGS) technology, with the ability to sequence many genomic regions at once, can provide clinicians with increased information, in the form of more mutations detected. Discussions on broad testing technology have largely been focused on incidental findings, or unanticipated results related to diseases beyond the primary indication for testing. By examining multiple genes that could be responsible for the patient’s presentation, however, there is also the possibility of unexpected results that are related to the reason genetic testing was ordered. We present a case study where multiple potentially causative mutations were detected using NGS technology. This case raises questions of scientific uncertainty, and has important implications for medical management and secondary studies. Clinicians and genetic counselors should be aware of the potential for increased information to affect one’s understanding of genetic risk, and the pre- and post-testing counseling process.     

Next Generation Sequencing is the Impetus for the Next Generation of Laboratory-Based Genetic Counselors

Next generation sequencing (NGS) is dramatically increasing the number of clinically available genetic tests and thus the number of patients in which such testing may be indicated. The complex nature and volume of the reported results requires professional interpretation of the testing in order to translate and synthesize the meaning and potential benefit to patients, and genetic counselors are uniquely suited to provide this service. The increased need for genetic counselors in this role, coupled with the time required and a limited number of trained and available counselors presents a challenge to current models for making genetic testing available to patients and their healthcare providers effectively and efficiently. The employment of genetic counselors at genetic/genomic laboratories is one model to expand the resources for providing this service. In this article, we briefly review the advent of NGS and its clinical applications, examine the core skills of genetic counselors and delineate the expanding roles and responsibilities of laboratory-based genetic counselors. We also propose changes to the genetic counseling training program curriculum to account for the increasing opportunities for genetic counselors to contribute and thrive within genetic testing laboratories.     

Collaboration of Colorado Cancer Genetic Counselors to Integrate Next Generation Sequencing Panels into Clinical Practice

The recent introduction of clinically available next generation sequencing (NGS) cancer panels has presented new challenges for genetic counselors. Determining which patients are appropriate for NGS panel testing is complex. Due to the large number of genes included in the NGS panels, thorough and appropriate pre-test counseling and interpretation of NGS results can be a time-consuming and difficult process. Many of the genes associated with increased cancer risk lack published clinical management guidelines and estimates of cancer risk for individuals with deleterious mutations. In order to efficiently and effectively review the clinical utility of NGS panels, Colorado cancer genetic counselors formed a working group to gain a better understanding of the genes included in NGS cancer panels. This publication reports on the approach of this group, the process used to evaluate a selected NGS panel, future directions for this collaboration, and ideas for other genetic counselors to form similar groups to efficiently evaluate new technologies and improve practice.     

Genetic Counseling Practice in Next Generation Sequencing Research: Implications for the Ethical Oversight of the Informed Consent Process

The potential for next generation sequencing research (NGS) to generate individual genetic results could have implications for the informed consent process and the provision of genetic counseling. We undertook a content analysis of informed consent templates and guidelines produced by Canadian institutional review boards, purposively sampling documents used by researchers to obtain consent from participants in genetics studies. Our goal was to examine the extent to which the informed consent documents addressed genetic counseling and the return of individual genetic results. Our analysis reveals that the majority of informed consent documents did not mention genetic counseling while several did not mention the return of results. We found differences in the ways in which documents addressed availability of counseling, eligibility criteria for referral to a genetic counselor, genetic counselor involvement, provision of services to family members of participants and incidental findings. From an ethical standpoint, consent documents should provide appropriate information so that participants may make an informed decision about their participation in research. The need to ensure adequate counseling for study populations in an NGS research context will necessarily involve adapting values that underlie care in genetic counseling practice. If the interests of research participants are to be truly promoted, the drafting and review of informed consent documents should give proper due to genetic counseling.     

The Impact of Breast Cancer Genetic Risk Assessment on Intentions to Perform Cancer Surveillance Behaviors

One hundred and fifty-four women undergoing breast/ovarian cancer genetic risk assessment completed questionnaires at entry into the Cancer Genetic Service for Wales (CGSW) assessment program and following risk provision, mapping the strength of intentions to engage in a number of preventive/surveillance behaviors, including seeing specialists, breast self-examination, and involvement in screening programs, including mammography. A number of potential predictors of intentions were also assessed, including participants' mood and emotional response to receiving risk information, the perceived benefits (in terms of reassurance and early disease detection) of engaging in each preventive behavior, and the perceived desires of their family and General Practitioner. Intentions to self-examine did not change following risk provision, although strength of intentions to engage in some other preventive behaviors did lessen. Family and General Practitioners appeared to be strong social influences on behavioral intentions, as were the perceived benefits of gaining reassurance and/or early detection of disease.     

Family History of Pancreatic Cancer in a High-Risk Cancer Clinic: Implications for Risk Assessment

Detailed family history is a critical element of cancer risk assessment. The relative importance of pancreatic cancer (PC) in a close family member, particularly in hereditary breast-ovarian syndrome (HBOS), is not clearly defined. We use a case-control design to investigate the importance of a family history of PC to cancer risk assessment. Case and control families were identified from the University of Chicago Cancer Risk database (1994–2005). Pedigrees were analyzed for personal and familial clinical cancer data. Cases included all new subjects (probands) reporting a close relative (first or second degree) with PC. Controls included the probands enrolled in the database immediately prior to and subsequent to each case (i.e. two controls for each case). From 1,231 pedigrees, 103 PC were reported by the proband in 87 unique families. Many probands reported multiple or early-onset PCs: one third (28/87) of case families met criteria for a familial PC syndrome [≥2 first-degree relatives with PC (n = 10) or PC diagnosed ≤50 (n = 18)]. Of these families, the majority (75%) concurrently met criteria suggestive of hereditary breast-ovarian syndrome (HBOS). Because of a family history consistent with HBOS, at least one individual from each of 29 case and 55 control families underwent genetic testing for BRCA1/2. Among case families, 19 of 29 (66%) had a BRCA1/2 mutation compared with 16 of 55 (29%) controls. A significant association between family history of PC and a BRCA1/2 mutation was seen (OR 3.78, 1.32–10.9). This point estimate was strengthened but less precise in the non-Ashkenazi Jewish subset of tested families (OR 6.03, 1.68–22.14). In a high-risk population, a family history of PC, though infrequently reported, is nonetheless clinically meaningful. In risk assessment for HBOS, identifying a family history of PC should strongly raise the suspicion of an unrecognized BRCA1/2 mutation.     

分化型甲状腺癌的风险评估和个体化治疗策略

甲状腺癌是内分泌系统最常见的恶性肿瘤,它的发病率正逐年增加,其中90％是分化型甲状腺癌,分化型甲状腺癌诊治方面存在很多争议,如分化型甲状腺癌的原发癌症的切除范围、是否行淋巴结清扫及清扫范围.根据甲状腺癌的风险评估实施个体化治疗,是分化型甲状腺癌未来的治疗方向.     

Teaching the History of Counseling: Training the Next Generation

The authors describe a teaching activity using a poster-session format to teach first-year counseling psychology doctoral students the history of counseling. Evaluative data suggest that the format was an effective and powerful tool to teach beginning counseling psychology students the history of the profession. The implications of the evaluative feedback are discussed in terms of teaching and preparing the next generation of counselors.     

Models of Service Delivery for Cancer Genetic Risk Assessment and Counseling

Increasing awareness of and the potentially concomitant increasing demand for cancer genetic services is driving the need to explore more efficient models of service delivery. The aims of this study were to determine which service delivery models are most commonly used by genetic counselors, assess how often they are used, compare the efficiency of each model as well as impact on access to services, and investigate the perceived benefits and barriers of each. Full members of the NSGC Familial Cancer Special Interest Group who subscribe to its listserv were invited to participate in a web-based survey. Eligible respondents were asked which of ten defined service delivery models they use and specific questions related to aspects of model use. One-hundred ninety-two of the approximately 450 members of the listserv responded (42.7 %); 177 (92.2 %) had provided clinical service in the last year and were eligible to complete all sections of the survey. The four direct care models most commonly used were the (traditional) face-to-face pre- and post-test model (92.2 %), the face-to-face pretest without face-to-face post-test model (86.5 %), the post-test counseling only for complex results model (36.2 %), and the post test counseling for all results model (18.3 %). Those using the face-to-face pretest only, post-test all, and post-test complex models reported seeing more new patients than when they used the traditional model and these differences were statistically significantly. There were no significant differences in appointment wait times or distances traveled by patients when comparing use of the traditional model to the other three models. Respondents recognize that a benefit of using alternative service delivery models is increased access to services; however, some are concerned that this may affect quality of care.     

Unethical Practice as Perceived by Mental Health Professionals: The Next Generation

Replicating a study done 15 years ago, the authors mailed a survey to psychiatrists, psychologists, psychotherapists, and marriage and family counselors who were listed in the San Antonio Yellow Pages to get information about their perceptions of the incidence of unethical practice. Results show a shift in perceived unethical practice over the 15-year time frame.     

Next Generation Sequencing in the Clinic: a Patterns of Care Study in a Retrospective Cohort of Subjects Referred to a Genetic Medicine Clinic for Suspected Lynch Syndrome

Next generation sequencing (NGS) gene panels are increasingly used in medical genetics clinics for the evaluation of common inherited cancer syndromes, but the clinical efficacy of these tests, and the factors driving clinical providers to order them are unclear. We conducted a patterns-of-care study to compare patients evaluated with NGS gene panels with a reference group. We abstracted demographic, socioeconomic, and clinical information in a retrospective cohort of patients referred to a large medical genetics clinic for evaluation of inherited colorectal cancer and polyposis syndromes. Patients tested with NGS gene panels were more likely to be insured compared to the reference group (85.3 % vs. 69.2 %, p = 0.0068),less likely to have prior tumor tissue testing (29.4 % vs. 54.3 %, p = 0.0004), and less likely to have an abnormal tumor tissue test result (46.7 % vs. 74.5 %, p = 0.01). No significant differences were found between groups in age, gender, race, employment status, personal history of colorectal cancer, or proportion of patients fulfilling Lynch syndrome clinical criteria. Patients with NGS testing were less likely to have a pathogenic/likely pathogenic variant detected (13.7 % vs. 31.9 %, p = 0.002). Patients referred for NGS testing to evaluate inherited colorectal cancer/polyposis risk appear to undergo tumor tissue testing less frequently than non-NGS testing patients. Further studies are needed to assess the most effective and cost-effective approach to genomic diagnosis in this patient population.