Abstract | INTRODUCTION:
Acute intermittent porphyria (AIP) is a very rare (orphan) metabolic disorder of porphyrin biosynthesis which is characterized by elevated plasma and urine levels of 5-aminolevulinic acid (5-ALA) and porphobilinogen (PBG). Patients with this disorder which is caused by a germline mutation of the hydroxymethylbilan-synthase (HMBS)-gene have a high risk of primary liver cancer which may be determined by disease activity. The exact mechanism of carcinogenesis of this rare tumor is unknown, however. MATERIALS AND METHODS: We analyzed paraffin-embedded formalin-fixed liver tumor and normal liver specimens of two female AIP patients treated at the Munich EPNET center. One patient had developed hepatocellular carcinoma (HCC), the other intrahepatic cholangiocarcinoma (CCA). Since biallelic inactivation of HMBS had been observed in one study, we used Sanger and next-generation sequencing with a 8 gene porphyria panel plus 6 potential modifier loci to search for mutations in DNA extractions. RESULTS: In the patient with the HCC, we found a second inactivating mutation in the HMBS gene in the tumor but not in the adjacent normal liver tissue. No mutation could be found in the liver tissues of the patient with CCA, however. CONCLUSIONS:
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Authors | Thomas Haverkamp, Olivia Bronisch, Thomas Knösel, Carolin Mogler, Wilko Weichert, Thomas Stauch, Claudia Schmid, Claudia Rummeny, Maria K Beykirch, Petro E Petrides |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 149
Issue 6
Pg. 2647-2655
(Jun 2023)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 36245063
(Publication Type: Case Reports, Journal Article, Review)
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Copyright | © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. |
Chemical References |
- Aminolevulinic Acid
- Flavoproteins
- Mitochondrial Proteins
- Porphyrins
- PPOX protein, human
- Protoporphyrinogen Oxidase
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Topics |
- Female
- Humans
- Aminolevulinic Acid
(urine)
- Carcinogenesis
- Carcinoma, Hepatocellular
(genetics)
- Flavoproteins
- Liver Neoplasms
(genetics)
- Mitochondrial Proteins
- Porphyria, Acute Intermittent
(genetics, pathology)
- Porphyrins
- Protoporphyrinogen Oxidase
(genetics)
- Adult
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