Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Corrigendum: Clinical Application of Multigene Panels: Challenges of Next-Generation Counseling and Cancer Risk Management

Background: Multigene panels can be a cost- and time-effective alternative to sequentially testing multiple genes, especially with a mixed family cancer phenotype. However, moving beyond our single-gene testing paradigm has unveiled many new challenges to the clinician. The purpose of this article is to familiarize the reader with some of the challenges, as well as potential opportunities, of expanded hereditary cancer panel testing. Methods: We include results from 348 commercial multigene panel tests ordered from January 1, 2014, through October 1, 2014, by clinicians associated with the City of Hope’s Clinical Cancer Genetics Community of Practice. We also discuss specific challenging cases that arose during this period involving abnormalities in the genes: CDH1, TP53, PMS2, PALB2, CHEK2, NBN, and RAD51C. Results: If historically high risk genes only were included in the panels (BRCA1, BRCA2, MSH6, PMS2, TP53, APC, CDH1), the results would have been positive only 6.2% of the time, instead of 17%. Results returned with variants of uncertain significance (VUS) 42% of the time. Conclusion: These figures and cases stress the importance of adequate pretest counseling in anticipation of higher percentages of positive, VUS, unexpected, and ambiguous test results. Test result ambiguity can be limited by the use of phenotype specific panels; if found, multiple resources (the literature, reference laboratory, colleagues, national experts, and research efforts) can be accessed to better clarify counseling and management for the patient and family. For pathogenic variants in low and moderate risk genes, empiric risk modeling based on the patient’s personal and family history of cancer may supersede gene-specific risk. Commercial laboratory and patient contributions to public databases and research efforts will be needed to better classify variants and reduce clinical ambiguity of multigene panels

Age-Friendly Communities Initiative:Public Health Approach to Promoting Successful Aging

Older adults consistently prefer aging in place, which requires a high level of community support and services that are currently lacking. With a rapidly aging population, the present infrastructure for healthcare will prove even more inadequate to meet seniors' physical and mental health needs. A paradigm shift away from the sole focus on delivery of interventions at an individual level to more prevention-focused, community-based approaches will become essential. Recent initiatives have been proposed to promote healthy lifestyles and preventive care to enable older adults to age in place. Prominent among these are the World Health Organization's Global Age-Friendly Communities (AFC) Network, with 287 communities in 33 countries, and AARP's Network of AFCs with 77 communities in the United States. In an AFC, older adults are actively involved, valued, and supported with necessary infrastructure and services. Specific criteria include affordable housing, safe outdoor spaces and built environments conducive to active living, inexpensive and convenient transportation options, opportunities for social participation and community leadership, and accessible health and wellness services. Active, culture-based approaches, supported and developed by local communities, and including an intergenerational component are important. This article provides a brief historical background, discusses the conceptualization of the AFC, offers a list of criteria, narrates case studies of AFCs in various stages of development, and suggests solutions to common challenges to becoming age-friendly. Academic geriatric psychiatry needs to play a major role in the evolving AFC movement to ensure that mental healthcare is considered and delivered on par with physical care