Claire Palles

Heterozygous germline MSH3 mutations, and probably MLH3 mutations, act as classical tumour suppressors, leading to excess somatic deletion mutations, signature ID4 and increased colorectal cancer risk

Germline haploinsufficiency for the base excision repair gene MUTYH causes mutational signature SBS18 in multiple tumour types, specifically leading to an increased risk of colorectal cancer

This study shows that germline MUTYH haploinsufficiency increases mutational signature SBS18 and CRC risk, but not other cancers, due to oxidative DNA damage in the colorectum.

Single cell analysis of Barrett's esophagus and carcinoma reveals cell types conferring risk via genetic predisposition

The paper uses single cell RNA-sequencing and genome-wide association study data to identify cell types and processes involved in Barrett's esophagus and esophageal adenocarcinoma risk.

Clinical syndromes linked to biallelic germline variants in MCM8 and MCM9

This study identifies biallelic germline variants in MCM8 and MCM9 as linked to polyposis, gastric cancer, early-onset colorectal cancer, and hypogonadism, with MCM9 variants showing stronger associations.

The metaplastic precursor state to oesophageal adenocarcinoma represents reversion to a transient epithelial cell state in the developing oesophagus

The paper identifies a metaplastic precursor state in Barrett's oesophagus as a reversion to a fetal epithelial cell state, revealing HNF4A's role and GWAS SNPs in regulatory regions.

Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls

This study uses Mendelian randomisation to identify causal risk factors for eight cancers, finding both well-established and novel molecular factors.

Elevated somatic mutation burdens in normal human cells due to defective DNA polymerases

The paper shows that germline mutations in POLE or POLD1 lead to elevated mutation burdens in normal human cells and tissues, but do not cause premature aging or other phenotypic features beyond early-onset cancer.

Germline loss-of-function variants in the base-excision repair gene MBD4 cause a Mendelian recessive syndrome of adenomatous colorectal polyposis and acute myeloid leukaemia