A number types of extracellular DNA (eg, cell-free, cfDNA) circulate in human blood, including mitochondrial, transcriptome, and regulatory DNA, usually at low concentrations. Larger amounts of cfDNA appear in any inflammatory condition, including organ damage due to a variety of reasons. The role of cfDNA in solid organ transplantation is discussed in this review as a valuable additional tool in the standard of care of transplant patients. Post-transplant monitoring requires the use of high-quality biomarkers for early detection of graft damage or rejection to be able to apply early therapeutic intervention. CfDNA complements the traditional monitoring strategies, being a risk stratification tool and an important prognostic marker. However, improving the sensitivity and specificity of cfDNA detection is necessary to facilitate personalized patient management, warranting further research in terms of measurement, test standardization, and storage, processing, and shipping. A diagnostic test (Allosure, CareDx, Inc., Brisbane, CA) for kidney, heart and lung transplant patients is now commercially available, and validation for other organs (eg, liver) is pending. To date, donor-derived cfDNA in combination with other biomarkers appears to be a promising tool in graft rejection as it is minimally invasive, time-sensitive, and cost-effective. However, improvement of sensitivity and specificity is required to facilitate personalized patient management. Whether it could be an alternate to graft biopsy remains unclear.

The CAN.HEAL consortium, comprising 47 cancer centers and academic institutions across 17 EU countries, has developed a set of recommendations for Molecular Tumor Boards (MTBs) to address the lack of standardized guidelines in personalized cancer medicine. Over the past 2 years, through extensive collaboration and seven dedicated online meetings, CAN.HEAL experts developed consensus-based recommendations across 10 critical domains. The consortium agreed that MTBs' primary role is to perform molecular and clinical assessments for patients requiring care beyond standard treatment. Core MTB composition should include medical oncologists, molecular biologists, pathologists, and bioinformaticians. Patient eligibility criteria should prioritize performance status, with flexibility for rare cases. Shared informed consent is crucial for sample collection, data use, and research. A two-tiered IT workflow, with minimal and maximal datasets, is recommended, along with a comprehensive decision support tool. These recommendations focus on genomic testing, acknowledging diversity of NGS assays and proposing general guidelines. MTB reports should be concise, with technical details provided in the molecular diagnostic report. Innovative approaches like the Drug Rediscovery Protocol support access to off-label therapies. Harmonized training for MTB members is essential to bridging knowledge gaps in this evolving field. Indicators are needed to assess MTB effectiveness over time. Expanding MTB benefits to underserved populations depends on creating a shared European MTB database. Standardizing MTB practices represents a key step toward equitable access to personalized medicine and improved cancer care across Europe. Sustainable implementation requires coordinated EU efforts, and dynamic MTBs that continuously refine genomic-driven decisions within real-world contexts.

Background: Brachydactylies are a group of inherited conditions, characterized mainly by the presence of shortened fingers and toes. Based on the patients’ phenotypes, brachydactylies have been subdivided into 10 subtypes. In this study, we have identified a family with two members affected by brachydactyly type A2 (BDA2). BDA2 is caused by mutations in three genes: BMPR1B, BMP2 or GDF5. So far only two studies have reported the BDA2 cases caused by mutations in the BMPR1B gene.Methods: We employed next‐generation sequencing to identify mutations in culpable genes.Results and Conclusion: In this paper, we report a case of BDA2 resulting from the presence of a heterozygous c.1456C>T, p.Arg486Trp variant in BMPR1B, which was previously associated with BDA2. The next generation sequencing analysis of the patients’ family revealed that the mutation occurred de novo in the proband and was transmitted to his 26‐month‐old son. Although the same variant was confirmed in both patients, their phenotypes were different with more severe manifestation of the disease in the adult.

Premature myocardial infarction (MI) risk factors, including genetic ones, are crucial for an individual risk stratification. The aim of this study was to investigate the role of genetic variants in young patients with MI and a family history of premature atherosclerosis (FHpa). The studied group consisted of 70 patients aged 26–49 (mean 43.1, SD ± 4.3; 17 women, 53 men), with MI and with FHpa. The targeted enrichment library was prepared and analyzed using the Next-Generation Sequencing method. The results of sequencing were compared to data from the reference control population, consisting of 597 people with no history of MI (418 women, 179 men) aged 18–83 (mean 40.5, SD ± 12.4), using Propensity Score Matching. SYNE1 gene variant NM_182961.4:c.20396+22A>G occurs with a significantly higher incidence in the studied group compared to the control population (OR 4.80 95%CI 1.43–14.45; p = 0.005) as a whole and when matched by age and gender (OR 9.31 95%CI 1.64–95.41; p = 0.004). There were no statistically significant differences in the incidence of variants related to familial hypercholesterolemia (LDLR NM_001195800.2:c.667G>A, PCSK9 NM_182961.4:c.658−36G>A NM_174936.3:c.658−36G>A, and APOB NM_000384.3:c.12382G>A) between both cohorts. A novel variant of the SYNE1 gene is associated with MI in young patients with FHpa.

Differentiated thyroid cancers (DTCs) are malignancies with ill-defined hereditary predisposition. Some germline variants influencing the risk of DTCs localize in disrupted in renal carcinoma 3 ( DIRC3 ), a poorly characterized long non-coding RNA (lncRNA) gene. Here, we characterized the function of DIRC3 in DTCs. We established that DIRC3 is downregulated in DTCs, and its high expression may reduce the risk of cancer recurrence in patients. DIRC3 transcripts were enriched in cell nuclei in vitro , where they upregulated insulin-like growth factor binding protein 5 ( IGFBP5 ), a gene known to modulate the cellular response to insulin-like growth factor 1 (IGF-1). Silencing of DIRC3 in thyroid cancer cell lines produced a phenotypic dichotomy: it augmented cell migration and invasiveness, reduced apoptosis, but abrogated the MTT reduction rate. We demonstrated that the pro-migratory phenotype was produced by the downregulation of IGFBP5 . Transcriptomic profiling confirmed a functional redundancy in the activities of DIRC3 and IGFBP5 . Moreover, downregulation of DIRC3 enhanced the susceptibility of cancer cells to IGF-1 stimulation and promoted Akt signaling. In conclusion, DIRC3 expression alters the phenotype of thyroid cancer cells and modulates the activity of IGFBP5/IGF-1/Akt axis. We propose an interplay between DIRC3 and IGF signaling as a mechanism that promotes thyroid carcinogenesis.