Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction.

Background: The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.