Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos: Cancer Genetics

G. Brandi, M. Deserti, A. Palloni, D. Turchetti, R. Zuntini, F. Pedica, G. Frega, S. De Lorenzo, F. Abbati, A. Rizzo, M. Di Marco, F. Massari, S. Tavolari

Research output: Contribution to journalArticlepeer-review


BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations. © 2020 The Authors
Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalCancer Genet.
Publication statusPublished - 2020


  • Asbestos
  • BAP1 germline mutation
  • Cholangiocarcinoma
  • asbestos
  • cisplatin
  • fluorouracil
  • gemcitabine
  • irinotecan
  • oxaliplatin
  • BAP1 protein, human
  • carcinogen
  • tumor suppressor protein
  • ubiquitin thiolesterase
  • adult
  • allele
  • anamnesis
  • Article
  • BAP1 gene
  • bile duct carcinoma
  • cancer cell
  • cancer combination chemotherapy
  • cancer radiotherapy
  • cancer tissue
  • carcinogenesis
  • case report
  • clinical article
  • computer assisted tomography
  • exon
  • female
  • gene
  • gene expression
  • gene sequence
  • germline mutation
  • heterozygosity loss
  • human
  • human tissue
  • immunohistochemistry
  • laparoscopic surgery
  • liver resection
  • lymph node dissection
  • middle aged
  • multiplex ligation dependent probe amplification
  • occupational exposure
  • priority journal
  • protein depletion
  • risk factor
  • RNA splice site
  • tumor suppressor gene
  • bile duct cancer
  • genetic predisposition
  • genetics
  • pathology
  • prognosis
  • Bile Duct Neoplasms
  • Carcinogens
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Prognosis
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase


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