PMS2 (PMS1 protein homolog 2)

In our cohort, the addition of MLPA provided an incremental yield of seven pathogenic CNVs, representing an 11.6% absolute increase in diagnostic sensitivity (from 16.7% to 28.3%) over the NGS-alone workflow, with CNVs accounting for 41% of all pathogenic findings. Our results show that MLPA is a very useful method in molecular diagnostics of LS and its implementation in routine genetic testing in combination with NGS using multigene panel testing would benefit both patients and health care providers.

This case underscores the importance of comprehensive assessment integrating tumor and germline molecular data, particularly when clinical or molecular findings are atypical or discordant. The digenic etiology also raises questions regarding cancer surveillance and management strategies in such individuals.

Comprehensive molecular profiling can help guide personalized immunotherapy decisions. Further studies are needed to confirm long-term benefits, optimize treatment duration and dosing, and identify predictive biomarkers for high-risk CRC.

While not significantly associated with tumor grade or patient demographics, MMRD may have clinical relevance in specific subgroups. NGS findings highlight the potential utility of integrating molecular diagnostics for identifying MSI and guiding immunotherapy decisions.

Six PMS2 variants were associated with either early or later-onset CMMRD. Future validation through larger prospective cohort studies is necessary to confirm our findings and better understand the natural history of PMS2-CMMRD to inform clinical decision-making in PMS2-Lynch syndrome (PMS2-LS).

These data highlight the importance of dMMR testing in patients with advanced solid tumors in China to optimize biomarker testing and treatment decisions.

IHC testing can discriminate between sporadic and MTS-associated sebaceous neoplasms, but diagnostic utility is limited by low specificity. Most MMR-deficient cases are not due to MTS.

In the studied population, dMMR tumors more frequently exhibited adverse prognostic features of EC, such as advanced stage of disease and lymphovascular space invasion. This suggests the potential for effective immunotherapy in this patient group.

Updated testing enabled more accurate diagnoses and personalized surveillance recommendations as well as identification of at-risk relatives. Given the improved diagnostic yield, it is crucial to consider genetic testing for individuals with unexplained polyposis who have previously undergone limited testing, due to small gene lists and/or outdated technology, ensuring alignment with current standards.

Most cases lack germline MMR mutations in normal tissues but harbor somatic MMR mutations in tumor tissues. Germline or somatic mutations in other genes related to MMR function may be observed in some cases.

Only 30 cases of NETs in LS have been described in the literature, most of them of gastrointestinal origin. We describe the first bronchopulmonary NET in a patient with LS, broadening the spectrum of LS tumours, and the first ACTH-producing tumour in LS.

The new deep-learning model accurately identified MMR status using macroscopic specimen images and showed potential for MMR screening among CRC patients, particularly in a rapid-response scenario.