MLH1 deletion

Our finding suggested that although NGS technologies have increased variant detection yield, combined approaches were still needed for complex variant characterization and pathogenicity assessment.

Deletion of MMR proteins and expression of PD-L1 are closely related to clinicopathological characteristics and overall prognosis of CRC patients. This suggests the relevance of MMR and PD-L1 as potential biomarkers for treatment of CRC patients.

Background: TMZ-induced G:T mismatches trigger MMR to perform futile repair of O6-methylguanine leading to apoptosis. Up to half of GBM patients have MMRD caused by pathway dysregulation. Biosimulation of MMRD predicts early progression on TMZ, echoing the long-held observation that TMZ does not trigger apoptosis in MMRD cancers. The study also reports inferior OS for MMRD compared to the historical experience of unmethylated-MGMT patients, suggesting that TMZ-induced hypermutation may compromise survival.

dMMR GC patients tended to be early stage, and the prognosis of those with early-stage GC was better. dMMR GC patients with vascular tumor thrombus or >6 LN metastases had a high recurrence rate and poor survival outcome.

In vitro evaluation of cell viability revealed the low nanomolar IC 50 of quisinostat (50nM) and romidepsin (2nM). Transcriptomic and proteomic investigations are underway to identify the mechanism of action underlying quisinostat-induced cytotoxicity. Ultimately, we are the first to demonstrate in vivo efficacy of the HDACi quisinostat against hypermutant DIPG, supporting further investigation and clinical advancement.

We highlight the role of tumor associated effector CD4+ T cells in pre-clinical models and patients with impaired APM. Overall, our findings highlight that the absence of B2M in MMRd cancers, does not prevent clinic response to immune checkpoint blockade.

Our results show that dMMR status may be more likely exist in female and younger (≤55 years) patients with a greater tumor burden (>5cm), right colon, T4 stage disease, poor differentiation and mucinous adenocarcinoma. Loss of PMS2 and MLH1 is the most common pattern of MMR protein expression deficiency, followed by concurrent deletion of MSH2 and MSH6.

She received carboplatin and paclitaxel, with initial clinical improvement, but then died within 3 months after diagnosis. This case highlights that thymic cancer may be one of the malignancies associated with Lynch syndrome, and MLH1 gene mutation may have a role in the pathogenesis of thymic cancer.

The accumulation of analyses with multigene testing will increase the available data for cancer predisposition genes in hereditary gastrointestinal cancer/polyposis. Educational campaigns for prevention, efficient screening programs, and more personalized care based on the profile of individual patients are necessary.

The main type of dMMR is co-deletion of MLH1 and PMS2 in patients with colorectal cancer. dMMR colorectal cancer has typical clinicopathological features and a lower incidence in China than in Western countries. The results of immunohistochemistry and PCR-CE are highly consistent for detecting dMMR in colorectal cancer patients.

There were some differences in the number of specific mutations in the families of different LS-related EC proband. HNRNPCL1, PRAMEF1, CFAP74, and DFFB may be potential biomarkers for EC or LS-related EC.