Hereditary cancer testing in a diverse sample across three breast imaging centers.

PURPOSE: Up to 10% of all breast cancers (BC) are attributed to inherited pathogenic variants (PV) in BC susceptibility genes; however, most carriers of PVs remain unidentified. Here, we sought to determine the yield of hereditary cancer gene PVs among diverse women attending breast imaging centers, who could benefit from enhanced surveillance and/or risk reduction interventions. METHODS: This cross-sectional retrospective cohort study included consecutive women, unselected for personal or family cancer history, who were offered genetic testing for hereditary cancer genes at the time of breast imaging at three centers (November 2020-March 2022). RESULTS: Among 1943 patients (median age: 66 years), self-reported race/ethnicity was White (34.5%), Hispanic (27.7%), African American (17.9%), Asian (4.5%), Ashkenazi Jewish (0.6%), Other (3.5%), and missing (13.0%). Thirty-nine patients (2%) were identified as carriers of a PV in an autosomal dominant clinically actionable hereditary breast and ovarian cancer (HBOC)-related or Lynch syndrome gene, most frequently, BRCA2 (6/39; 15.4%), PALB2 (8/39; 20.5%), CHEK2 (10/39; 25.6%), and PMS2 (5/39; 12.8%). Of the 34 PVs with known race/ethnicity, 47% were detected among non-White patients. Overall, 354/1,943 (18.2%) of patients met NCCN guidelines for HBOC gene testing and only 15/39 (38.5%) patients with an autosomal dominant clinically actionable PV met guidelines. CONCLUSION: This population health approach extended the reach of genetic cancer risk assessment in a diverse population and highlighted the limits of a guideline-based approach. This may help address inequity in access to risk-appropriate screening and cancer prevention.

Heterologous Expression of CLIBASIA_03915/CLIBASIA_04250 by Tobacco Mosaic Virus Resulted in Phloem Necrosis in the Senescent Leaves of Nicotiana benthamiana.

Huanglongbing (HLB), also known as citrus greening, is the most notorious citrus disease worldwide. Candidatus Liberibacter asiaticus (CaLas) is a phloem-restricted bacterium associated with HLB. Because there is no mutant library available, the pathogenesis of CaLas is obscure. In this study, we employed tobacco mosaic virus (TMV) to express two mature secretion proteins CLIBASIA_03915 (m03915) and CLIBASIA_04250 (m04250) in Nicotiana benthamiana (N. benthamiana). Phloem necrosis was observed in the senescent leaves of N. benthamiana that expressed the two low molecular weight proteins, while no phloem necrosis was observed in the plants that expressed the control, green fluorescent protein (GFP). Additionally, no phloem necrosis was observed in the senescent leaves of N. benthamiana that expressed the null mutation of m03915 and frameshifting m04250. The subcellular localizations of m03915 and m04250 were determined by fusion with GFP using confocal microscopy. The subcellular localization of m03915 was found to be as free GFP without a nuclear localization sequence (NLS). However, m04250 did have an NLS. Yeast two-hybrid (Y2H) was carried out to probe the citrus proteins interacting with m03915 and m04250. Six citrus proteins were found to interact with m03915. The identified proteins were involved in the metabolism of compounds, transcription, response to abiotic stress, ubiquitin-mediated protein degradation, etc. The prey of m04250 was involved in the processing of specific pre-mRNAs. Identification of new virulence factors of CaLas will give insight into the pathogenesis of CaLas, and therefore, it will eventually help develop the HLB-resistant citrus.