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.

Effect of School HPV Vaccination Requirements on Pediatricians' Recommendations.

: Pediatrician recommendations are highly influential in parents' decisions to vaccinate their children against HPV. Unqualified, presumptive, and bundled recommendations (UPBRs) are associated with increased HPV vaccine uptake and are considered best practice. This study analyzes pediatricians' self-reported data to assess changes in UPBR use and the psychosocial determinants of UPBR use as a result of the implementation of a multi-level intervention, the Adolescent Vaccination Program (AVP).