Somatic HNF1A mutations in the malignant transformation of hepatocellular adenomas: A retrospective analysis of data from MSK-IMPACT and TCGA Journal Article


Authors: Hechtman, J. F.; Abou-Alfa, G. K.; Stadler, Z. K.; Mandelker, D. L.; Roehrl, M. H. A.; Zehir, A.; Vakiani, E.; Middha, S.; Klimstra, D. S.; Shia, J.
Article Title: Somatic HNF1A mutations in the malignant transformation of hepatocellular adenomas: A retrospective analysis of data from MSK-IMPACT and TCGA
Abstract: Mutations of Hepatocyte-Nuclear-Factor-1-Homeobox-A (HNF1A) gene and loss of Liver-Fatty-Acid-Binding-Protein (LFABP) are well documented in hepatocellular adenoma. However, the role of HNF1A mutations in hepatocellular carcinoma remains to be determined. In this study, all hepatocellular neoplasms evaluated by our institutional Memorial Sloan Kettering-Integrated Mutational Profiling of Actionable Clinical Targets assay or the Cancer Genome Atlas sequencing, and cases reported in the literature, were queried for HNF1A mutations. Together, 11 of 672 (1.6%) hepatocellular carcinomas harbored HNF1A mutations. The single case from our institution (n = 153) was extremely well differentiated, arising in a background of adenomatosis. Both the adenoma and carcinoma component contained the same 2 somatic HNF1A mutations (p. E32* and L214Q), with loss of LFABP. From the literature, 2 of 146 (1.4%) hepatocellular carcinomas had HNF1A mutations, and both arose in a background of adenomatosis. Information on pre-existing adenoma for the remaining cases (8/373, from The Cancer Genome Atlas) was not available. HNF1A mutations in carcinomas were associated with negative viral hepatitis status (p =.004), mutually exclusive with catenin beta-1 (CTNNB1) hotspot mutations, and trended to occur more in females (p =.06) and without cirrhosis (p =.03). Grade was not associated with HNF1A status (p =.28). Somatic HNF1A mutations occur in approximately 1% to 2% of hepatocellular carcinoma, often in a background of adenomatosis. Our findings suggest that malignant transformation of HNF1A-mutated hepatocellular adenoma occurs, albeit infrequently. Hepatocellular adenomas with HNF1A mutation or adenomatosis with loss of LFABP warrant thorough sampling and examination. © 2018 Elsevier Inc.
Keywords: hepatocellular carcinoma; malignant transformation; hnf1a; adenomatosis; lfabp
Journal Title: Human Pathology
Volume: 83
ISSN: 0046-8177
Publisher: Elsevier Inc.  
Date Published: 2019-01-01
Start Page: 1
End Page: 6
Language: English
DOI: 10.1016/j.humpath.2018.08.004
PROVIDER: scopus
PUBMED: 30121369
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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MSK Authors
  1. Ghassan Abou-Alfa
    203 Abou-Alfa
  2. Zsofia Kinga Stadler
    133 Stadler
  3. David S Klimstra
    816 Klimstra
  4. Jinru Shia
    438 Shia
  5. Ahmet Zehir
    132 Zehir
  6. Efsevia Vakiani
    160 Vakiani
  7. Sumit   Middha
    46 Middha
  8. Michael H Roehrl
    30 Roehrl