Childhood solid tumours

Gene: ERCC1

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 4 individuals from 3 families with childhood-onset hepatocellular carcinoma due to biallelic variants in this gene. Diagnosis may have treatment implications due to heightened sensitivity of individuals with ERCC1 variants to DNA-damaging agents.

Created: 1 Oct 2025, 11:09 a.m. | Last Modified: 1 Oct 2025, 11:09 a.m.

Panel Version: 5.6

ERCC1 is associated with a spectrum of DNA repair disorders from severe neonatal conditions (Cerebrooculofacioskeletal syndrome 4, OMIM:610758) to multisystem disorders (Xeroderma Pigmentosum) that can extend into adolescence and early adulthood.

Xeroderma Pigmentosum is associated with increased risk for skin cancer, but also solid tumours.

A recent study (PMID: 40684071) also identified seven individuals from five families carrying biallelic ERCC1 variants, who exhibited a distinct clinical phenotype including growth restriction, photosensitivity, and kidney and liver dysfunction. Hepatocellular carcinoma developed in four children, resulting in death in two. Older individuals exhibited additional features, including ataxia, basal cell carcinomas, pancreatic insufficiency, ovarian failure, hypothyroidism, and restrictive lung disease. Most reported individuals have (p.Arg156Trp) on at least one allele, often with a LOF variant in trans. Functional assays using patient-derived fibroblasts demonstrated significant destabilisation of the ERCC1-XPF complex and defects in NER and ICL repair.

Created: 1 Oct 2025, 10:51 a.m. | Last Modified: 1 Oct 2025, 10:51 a.m.

Panel Version: 5.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
xeroderma pigmentosum, MONDO:0019600; hepatorenal syndrome, MONDO:0001382

Publications

• 40684071

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Xeroderma Pigmentosa