SBS5 signature

With the largest IPN/ICPN cohort reported to date, our study provides a genome- and spatial transcriptome-level portrait of sequential carcinogenesis and differences in the anatomical location of biliary papillary neoplasms.

In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.

Our results imply that the detection of HRR gene mutations can predict recurrence in patients with UC. In addition, this study provides a path to explore the role of HRR-directed therapies, including PARPis, chemotherapy, and immunotherapy.

In contrast, MSA signature assignment showed a relative enrichment of the GA signature in the high ACR exposure (6 of 10 cases), compared to the low exposure patient group (3 of 10 cases).ConclusionOur results reveal for the first time GA mutagenesis in human renal cancer with documented dietary ACR exposure, indicating potential contributing effects of ACR. Upon confirmation in a larger sample set, these findings may have important implications for cancer prevention aimed at the reduction of human exposure to acrylamide.

This study represents the largest WES analysis to date of AA tumors. Importantly, while there are overlapping mutational signatures, suggesting similarity in the mutagenic process with CRC, distinct mutational differences between AA and CRC were noted.

Thus, unlike other cancers, BRAFV600E alone appears to suffice to induce malignant transformation in some HCLc. Additionally, SHM in non-Ig loci including BCL6 may implicate early traffic of the tumor cell of origin through the germinal center and early exit prior to acquisition of CD27, or mutational events at ectopic sites.

This is the first study to show a selective net loss of arginine codon usage in MM and its clinical impact on PFS. A targeted deprivation of Arginine in the tumor microenvironment is a potential therapeutic modality under trials in certain cancers but has not been deeply investigated in MM. The second novel finding of this study is identification of oncogene SPANXD as a potential driver of MM.

These results give an understanding of somatic changes and the mutational landscape associated with HNPGLs and are important for the identification of molecular mechanisms involved in tumor development.

We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.

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.