Community Genetics screening in a pandemic: solutions for pre-test education, informed consent, and specimen collection.

A Community Genetics carrier screening program for the Jewish community has operated on-site in high schools in Sydney (Australia) for 25 years. During 2020, in response to the COVID-19 pandemic, government-mandated social-distancing, 'lock-down' public health orders, and laboratory supply-chain shortages prevented the usual operation and delivery of the annual testing program. We describe development of three responses to overcome these challenges: (1) pivoting to online education sufficient to ensure informed consent for both genetic and genomic testing; (2) development of contactless telehealth with remote training and supervision for collecting genetic samples using buccal swabs; and (3) a novel patient and specimen identification 'GeneTrustee' protocol enabling fully identified clinical-grade specimens to be collected and DNA extracted by a research laboratory while maintaining full participant confidentiality and privacy.

Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants: Application of a points-based ACMG/AMP approach.

Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

Purpose: Tubo-ovarian cancer (TOC) is a sentinel cancer for and pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed.

Evaluation of two population screening programmes for founder mutations in the Australian Jewish community: a protocol paper.

Introduction: People of Ashkenazi Jewish (AJ) ancestry are more likely than unselected populations to have a pathogenic variant, which cause a significantly increased risk of breast, ovarian and prostate cancer. Three specific pathogenic variants, referred to as -Jewish founder mutations (B-JFM), account for >90% of pathogenic variants in people of AJ ancestry. Current practice of identifying eligible individuals for testing based on personal and/or family history has been shown to miss at least 50% of people who have one of these variants.

Implementing gene curation for hereditary cancer susceptibility in Australia: achieving consensus on genes with clinical utility.

Background: The strength of evidence supporting the validity of gene-disease relationships is variable. Hereditary cancer has the additional complexity of low or moderate penetrance for some confirmed disease-associated alleles.

Methods: To promote national consistency in interpretation of hereditary cancer/tumour gene test results, we requested opinions of representatives from Australian Family Cancer Clinics regarding the clinical utility of 157 genes initially collated for a national research project.

Online BRCA1/2 screening in the Australian Jewish community: a qualitative study.

Screening programmes for BRCA1/2 Jewish Founder mutations (JFM) in the Jewish community have been advocated internationally. Implementation of these programmes could decrease morbidity and mortality of BRCA1/2 JFM carriers through the uptake of cancer screening strategies and risk-reducing surgery. An online programme offered to the Sydney Jewish community that delivers pre-test information and collects consent for BRCA1/2 JFM testing via a website is currently being evaluated (JeneScreen).

The :p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes , , , , and are associated with breast cancer risk. , which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes.

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.

Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

This corrects the article DOI: 10.1038/bjc.2017.

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.

Improving attendance to genetic counselling services for gynaecological oncology patients.

Background: Gynaecological cancers may be the sentinel malignancy in women who carry a mutation in BRCA1 or 2, a mis-match repair gene causing Lynch Syndrome or other genes. Despite published guidelines for referral to a genetics service, a substantial number of women do not attend for the recommended genetic assessment. The study aims to determine the outcomes of systematic follow-up of patients diagnosed with ovarian or endometrial cancer from Gynaecologic-oncology multidisciplinary meetings who were deemed appropriate for genetics assessment.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.

Hereditary gynaecologic cancers in Nepal: a proposed model of care to serve high risk populations in developing countries.

Background: Endometrial, ovarian and breast cancers are paradigms for global health disparity. Women living in the developing world continue to present in later stages of disease and have fewer options for treatment than those in developed countries. Risk reducing surgery is of proven benefit for women at high risk of gynaecological cancer.

Lost in translation: returning germline genetic results in genome-scale cancer research.

Background: The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned.

Hereditary Ovarian Cancer and Risk Reduction.

Mutations in BRCA1 and BRCA2 account for hereditary breast and ovarian cancer syndrome in a majority of families and 14% of epithelial ovarian cancer cases. Despite next-generation sequencing, other identified genes (Lynch Syndrome, RAD51C, RAD51D, and BRIP1) account for only a small proportion of cases. The risk of ovarian cancer by age 70 is approximately 40% for BRCA1 and 18% for BRCA2.

Genetic testing in a gynaecological oncology care in developing countries-knowledge, attitudes and perception of Nepalese clinicians.

Background: Genetic testing for an inherited susceptibility to cancer is an emerging technology in medical practice. Little information is currently available about physicians' attitudes towards these tests in developing countries.

Methods: We conducted an email survey of Nepalese physicians practicing in academic and non-academic settings in Nepal, regarding knowledge, attitudes and perception towards genetic testing for gynaecologic cancer.

Changing patterns of referrals and outcomes of genetic participation in gynaecological-oncology multidisciplinary care.

Background: Genetic participation in gynaecological oncology multidisciplinary team meetings (MDT) may identify the sentinel cancer in women with hereditary breast-ovarian cancer syndrome or Lynch syndrome.

Aims: To identify the changing patterns of genetic referral from 2010 to 2014 and the outcomes of referrals through clinical MDT case review.

Materials And Methods: Medical records of cases of gynaecological cancer presented at the MDT meetings and genetics databases were reviewed to determine the frequency and outcomes of recommendations for genetic referral between 2010 and 2014.

Community attitudes towards a Jewish community BRCA1/2 testing program.

About 2.5 % of the Ashkenazi-Jewish population carry one of three "founder" mutations in BRCA1 and BRCA2 (BRCA1/2). Currently, testing is offered to Jewish people with a personal and/or family history of breast and/or ovarian cancer; however less than half of BRCA1/2 carriers within the Jewish population are aware of their family history.