KMT2D mutation

The results of multivariate Cox regression analysis showed that TET2 mutation (HR=8.483, 95%CI: 1.278-56.330) was a risk factor of SMF in JAK2V617F+ MPN patients. TET2 mutation is a risk factor for SMF in JAK2V617F+ MPN patients.

Patients with G12R mutations had longer OS compared to G12D overall (12.7 vs 10.1 months, p-value=0.0001), with similar trends in patients treated with gemcitabine/nab-paclitaxel (13.5 vs 10.4 months, p-value=0.0002) or FOLFIRINOX (18.3 vs 14.0 months, p-value<0.001)...Patients with G12D mutations had lower OS compared to G12R. Based on this data, future studies should address the KRAS mutation status and explore distinct therapeutic vulnerabilities.

The FOXL2 missense mutation was the only common somatic DNA alteration in aGCT. TERT promoter mutations were reported more frequently in recurrent aGCT but their clinical relevance remains uncertain. In contrast to previous reports, truncating KMT2D mutations were not found to be associated with recurrent aGCT. Evidence on common germline variants in aGCT is sparse. The role of somatic and germline DNA alterations in the development of other malignancies in women with aGCT remains uncertain. Further research involving matched primary and recurrent tumors, as well as other primary malignancies, is essential to better understand the mutations that drive tumor development.

We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular-pathological, clinical, and prognostic analysis correlating with prognosis.

We observed distinct mutation patterns and clinical factors between LUAD and LUSC, and noted that patients with TMB≥10 and PD-L1≥50% exhibited enhanced immunotherapy effects. Combining TMB≥10 and PD-L1≥50% proved to be a more effective predictor of immunotherapy efficacy.

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

TP53 mutations found in 82% of ovarian SCC cases. CDKN2A mutations and 9p21.3 loss observed in 54.5% of ovarian SCC cohort.

Our study thus illustrates how tumour suppressor gene LOF alterations can be exploited to reveal potentially targetable cancer cell vulnerabilities.

Through this endeavor, we identified two novel genes, CNTNAP5 and GATA6, implicated in CRC carcinogenesis. Overall, our findings reveal convincing biomarkers markers for detecting CRAs with a propensity for CRC development, highlighting the importance of early genetic screening in CRC prevention.

IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.

The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

P1, N=15, Active, not recruiting, Hugo W. Moser Research Institute at Kennedy Krieger, Inc. | Trial completion date: Dec 2024 --> Aug 2024