FAT4 mutation

The molecular landscape of CoM in Chinese patients was updated with new findings. A relatively high frequency of mutated FAT4 was determined in Chinese CoM patients, and decreased expression of FAT4 was found in patients with worse prognoses. In addition, both BRAF mutations and FAT4 mutations could serve as predictive factors for CoM patients.

In summary, our study highlighted the clinical implications of CSF-ctDNA in CNSi detection of ND DLBCL pts (Figure 1M): (1) CSF-ctDNA exhibits higher sensitivity than CM in detecting CNSi in ND DLBCL. (2) Different genomic and clinical landscapes were observed between SCNSL and PCNSL. (3) The CNSi-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNSi in ND DLBCL.

Gene co-occurrence survival analysis showed that mPFS of pts harboring FAT3/FAT4 mutations were significantly shorter than those without FAT3/FAT4 mutations (8.9 mo vs 16.5 mo, p=0.012). Conclusions Clinical utility of ctDNA was demonstrated, not only at baseline by identifying fusion types and subgroups of ALK+ NSCLC pts that may benefit more from SAF-189s, but also at progression by tracking ALK-resistant mutations.

However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

Our findings indicated that FAT4 mutation serves as a potential novel biomarker correlated with a better response to immunotherapy combined with anti-angiogenic therapy in MSS metastatic CRC, which may be related to the activation of CD4 T cell infiltration. However, these need to be validated by further cohort expansion.

Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor, and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies.