The ultrarare hepatoblastoma is the most common pediatric liver cancer.
HB risk is related to a few rare syndromes, and the molecular bases
remain elusive for most cases. We investigated the burden of rare
damaging germline variants in 30 Brazilian patients with HB. A high
frequency of prematurity (20%) and birth defects (37%), especially
craniofacial (17%, including craniosynostosis) and kidney (7%)
anomalies, was observed. Pathogenic or likely pathogenic variants mapped
to 10 cancer predisposition genes (APC, CHEK2, DROSHA, ERCC5, FAH, MSH2,
MUTYH, RPS19, TGFBR2 and VHL,) were detected in 33% of the patients,
only 40% of them with a family history of cancer. These findings showed
a predominance of CPGs with a known link to gastrointestinal/colorectal
and renal cancer risk. A remarkable feature was an enrichment of rare
damaging variants affecting different classes of DNA repair genes,
particularly those known as Fanconi anemia genes. Moreover, several
damaging rare variants mapped to genes impacting liver functions were
observed. To our knowledge, this is the first comprehensive assessment
of rare germline variants in HB patients, contributing to elucidating
the genetic architecture of HB risk.
Malignant pleural mesothelioma: Germline variants in DNA repair genes may steer tailored treatment
