On histological examination, three of the adenomas showed the typical morphology of HNF1-α inactivated adenomas, whereas one showed a myxoid adenoma morphology.
We identified the breakpoints for t(6;12)(p21.1;q24.31), disrupting HNF1A in a patient diagnosed with hepatic adenomas and maturity-onset diabetes of the young (MODY).
Genotypical classification of the adenomas has led to the identification of four subgroups that correlate genotype with phenotype: human hepatocyte nuclear factor-1 alpha (HNF1α) inactivating HCA, β-catenin activating HCA, inflammatory HCA and unclassified HCA.
Key features include metabolic alterations (induced by defects in HNF1A), oncogene-induced inflammation (activation of JAK-STAT signaling in inflammatory adenomas), and an association between activation of Wnt/β-catenin signaling and progression of HCAs in hepatocellular carcinomas.
Bi-allelic inactivation of TCF1 was found in 10 of 16 screened adenomas, and heterozygous germline mutation were present in three affected individuals.