PALB2 (Partner and localizer of BRCA2)

These findings advance understanding of pALL genetic architecture and inform future risk stratification.

Long considered undruggable due to its molecular structure, the advent of sotorasib and adagrasib has ushered in multiple novel therapeutics targeting the RAS pathway, including mutation-selective, pan-KRAS, and pan-RAS inhibitors. Here, we detail the different areas of investigation targeting KRAS and other precision-based therapies in PDAC, as well as the potential emerging roles of local interventions (radiation, surgery) for select patients with oligometastatic disease. Composite predictive biomarkers using genomic, proteomic, and radiographic factors are needed to refine and individualize treatment selection and ultimately improve patient outcomes.

However, uncertainties remain regarding the magnitude of benefit, eligibility criteria, surveillance start age, cost-effectiveness, and the risk of overdiagnosis. This review critically appraises current evidence, focusing on the Italian and European experience, evaluates the pros and cons of HRIs surveillance, and proposes updated criteria and considerations for a structured, registry-based national program aligned with new evidence.

Post hoc analyses suggested sufficient statistical sensitivity to detect the observed differences; however, results should be interpreted considering the retrospective, single-center design. These findings support the clinical value of incorporating non-BRCA genes into multigene testing strategies in Argentina and underscore the need for larger multi-center studies to confirm these observations and refine genetic counseling and surveillance strategies in Latin American populations.

Participants desired more follow-up, better support and education around practical and emotional considerations for prophylactic surgery, and acknowledgment of personal and community factors that impacted them. Genetic counselors can personalize each visit to the patient and their needs by extensively contracting and bringing up topics that may be relevant and adjusting based on their preferences and values.

This work lays the basis for precision and personalised treatment for TNBC patients. However, future optimisation and clinical validation of these nanoparticles can be done in future to determine their translational potential for use in practice.

Germline pathogenic variants in the HR pathway genes drive oncogenesis in a large subset of PAMPCAs. These findings highlight the importance of germline genetic testing for patients with PAMPCA for informing therapy and assessing familial risk.

and be estrogen receptor positive [p < 0.001] progesterone status positive [p < 0.001] and HER2 negative [p = 0.043]...This can help clinicians adapt when counseling these patients. Furthermore, ILC keeps its distinctive characteristics independent of the genetic backdrop.

This spliceogenic effect was reliably detectable only in cultured lymphocytes preferentially expressing the full-length FANCA transcript. Overall, short-term lymphocyte culture re-presents a simple and flexible RNA source that enhances variant interpretation in clinical RNA-seq analyses.

Among patients with a reported germline mutation, 36.1% had a BRCA1, 62.9% a BRCA2 and 1.0% a PALB2 mutation. In summary, outcomes were comparable to those reported in pivotal trials despite later-line use of PARP-inhibitors in this analysis.