MSH2 (MutS Homolog 2)

Lesion-specific molecular characterization combined with regional lymph node MMR phenotyping is critical for the precise management of SCRCs with discordant MMR status. This case provides a referable diagnostic workflow and surgical decision-making framework for this rare clinical scenario, supporting risk-adapted individualized therapy for molecularly heterogeneous colorectal cancer.

The patient's phenotype is consistent with SIX3 haploinsufficiency leading to severe forebrain division insufficiency; the adjacent MMR deletion defines the Lynch susceptibility locus. We emphasize the need to consider the risk of cancer in later life, in addition to the currently available findings.

Our findings demonstrate that MMR plays a pivotal role in gene amplification through mediating DSBs repair pathways and facilitating the formation of MN/NBUDs in ecDNA-containing cells. MMR is likely to emerge as a prime therapeutic target worthy of in-depth exploration in future clinical investigations.

SMAC-2 originated from a metastatic EDP-M-treated ACC in a female patient with hypercortisolism and hyperandrogenism, while SMAC-3 derived from a male patient with a mitotane-treated local recurrence, with no sign of hypercortisolism...Experiments were carried out to study the stability of the two cell lines. SMAC-2 and SMAC-3 display unique molecular and functional features, expanding the repertoire of experimental ACC models and representing valuable tools for preclinical research alongside established cell lines.

The benefit-cost ratio (BCR) analysis demonstrated the greater cost-effectiveness of genetic testing compared to endoscopic surveillance to all relatives at risk. Although our cohort is clinically enriched and does not reflect the population prevalence of LS in Southern Thailand, these findings highlight the substantial LS burden within high-risk families and underscore the importance of incorporating genetic screening, counseling, and tailored surveillance strategies into clinical practice.

Our study shows that MSI and neoantigen accumulation emerge during the evolution of precancerous lesions in LS. These findings support the clinical evaluation of Nous-209, a shared neoantigen vaccine, as an immunoprevention strategy for MSI-driven colorectal carcinogenesis, with important implications for cancer prevention research.

P=N/A, N=185, Terminated, Washington University School of Medicine | N=310 --> 185 | Trial completion date: Jan 2027 --> Mar 2026 | Recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Mar 2026; Loss of space for imaging

This exploratory analysis suggested a higher uptake of risk-reducing surgery at the safety-net hospital than at the university medical center. Understanding factors contributing to this difference will be critical to supporting gynecologic cancer risk management in Lynch syndrome.

MLH1 promoter methylation, MMR deficiency, and CDX2 are rare events in PTC and do not appear to influence PFS. Although infrequent, the expression of CDX2 is not exclusive to any PTC subtype.

P=N/A, N=289, Terminated, University Hospital, Rouen | Completed --> Terminated; Difficulty in enrolling patients

P1/2, N=13, Not yet recruiting, Radboud University Medical Center | N=23 --> 13

Even in patients desiring future fertility, rates of referral to REI (17%) and use of ART (8%) were low. Our findings demonstrate possible gaps in counseling and underutilization of fertility services for young mutation carriers.