title: BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype.
abstract: BACKGROUND
  BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined.
  
  
  METHODS
  The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed.
  
  
  RESULTS
  Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy.
  
  
  CONCLUSIONS
  BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated.
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Humaid O
authors: HO
authors: Al-Shamsi
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Deepa
authors: D
authors: Anand
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Rachna T
authors: RT
authors: Shroff
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Apurva
authors: A
authors: Jain
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Mingxin
authors: M
authors: Zuo
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Claudius
authors: C
authors: Conrad
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Jean-Nicolas
authors: JN
authors: Vauthey
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Milind M
authors: MM
authors: Javle
keywords: BAP1-mutant cholangiocarcinoma; Foundation Medicine; cisplatin; gemcitabine; next-generation sequencing (NGS)