Nuclear BAP1 loss is common in intrahepatic cholangiocarcinoma and a subtype of hepatocellular carcinoma but rare in pancreatic ductal adenocarcinoma

Mosbeh, Asmaa; Halfawy, Khalil; Abdel-Mageed, Wael S.; Sweed, Dina; Abdel‐Rahman, Mohamed H.

doi:10.1016/j.cancergen.2018.03.002

Cited by 20 publications

(10 citation statements)

References 40 publications

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“…Two previous studies demonstrated infrequent BAP1 loss in PDAC ranging from 0.33 to 2.4% (46,47). Similarly, we found BAP1 loss in 2% of the human PDAC samples evaluated ( Supplementary Fig.…”

Section: Discussionsupporting

confidence: 86%

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

Lee¹,

Pham²,

Chang³

et al. 2020

Cancer Research

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The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk for mesothelioma and melanocytic tumors. Here, we show that pancreatic intraepithelial neoplasia driven by oncogenic mutant KrasG12D progressed to pancreatic adenocarcinoma in the absence of BAP1. The Hippo pathway was deregulated in BAP1-deficient pancreatic tumors, with the tumor suppressor LATS exhibiting enhanced ubiquitin-dependent proteasomal degradation. Therefore, BAP1 may limit tumor progression by stabilizing LATS and thereby promoting activity of the Hippo tumor suppressor pathway. Significance: BAP1 is mutated in a broad spectrum of tumors. Pancreatic Bap1 deficiency causes acinar atrophy but combines with oncogenic Ras to produce pancreatic tumors. BAP1-deficient tumors exhibit deregulation of the Hippo pathway. See related commentary by Brekken, p. 1624

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Section: Discussionsupporting

confidence: 86%

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

Lee¹,

Pham²,

Chang³

et al. 2020

Cancer Research

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“…From a diagnostic point of view, these molecular alterations fairly restricted to iCCA can be used to improve the classification of anatomical ‘borderline cases’, for example, to discriminate perihilar from intrahepatic CCA. Additionally, BAP1 mutations were found to be restricted to iCCA in some studies and BAP1 and IDH mutations were also found in HCC, suggesting an overlap of iCCA, cHCC‐CCAs and HCC respectively a common cell‐of‐origin for at least some of these mass‐forming, small‐duct type iCCAs . As cHCC‐CCAs represent a separated tumour type, according to the current WHO classification, and mostly vary in their molecular profile significantly to iCCA, this will not be further discussed in this review .…”

Section: Current Problems In Diagnostic Pathology Of Ccamentioning

confidence: 99%

Anatomical, histomorphological and molecular classification of cholangiocarcinoma

Kendall

Verheij

Gaudio

et al. 2019

Liver International

254

210

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Cholangiocarcinoma constitutes a heterogeneous group of malignancies that can emerge at any point of the biliary tree. Cholangiocarcinoma is classified into intrahepatic, perihilar and distal based on its anatomical location. Histologically, conventional perihilar/distal cholangiocarcinomas are mucin‐producing adenocarcinomas or papillary tumours; intrahepatic cholangiocarcinomas are more heterogeneous and can be sub‐classified according to the level or size of the displayed bile duct. Cholangiocarcinoma develops through multistep carcinogenesis and is preceded by dysplastic and in situ lesions. Definition and clinical significance of precursor lesions, including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm, are discussed in this review. A main challenge in diagnosing cholangiocarcinoma is the fact that tumour tissue for histological examination is difficult to obtain. Thus, a major clinical obstacle is the establishment of the correct diagnosis at a tumour stage that is amenable to surgery which still represents the only curable therapeutic option. Current standards, methodology and criteria for diagnosis are discussed. Cholangiocarcinoma represents a heterogeneous tumour with regard to molecular alterations. In intrahepatic subtype, mainly two distinctive morpho‐molecular groups can currently be discriminated. Large‐duct type intrahepatic cholangiocarcinoma shows a high mutation frequency of oncogenes and tumour suppressor genes, such as KRAS and TP53 while Isocitrate Dehydrogenase 1/2 mutations and Fibroblast Growth Factor Receptor 2‐fusions are typically seen in small‐duct type tumours. It is most important to ensure the separation of the given anatomical subtypes and to search for distinct subgroups within the subtypes on a molecular and morphological basis.

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“…In addition to the classic malignancies associated with BAP1 hereditary tumor predisposition syndrome, other suspected, but unconfirmed, tumors include mammary carcinoma, cholangiocarcinoma, non‐small‐cell lung adenocarcinoma, meningioma, and neuroendocrine carcinoma . In the current case, the patient's mother had a history of cervical carcinoma at the age of 17 and her maternal grandfather had a history of colorectal carcinoma at the age of 70.…”

Section: Discussionmentioning

confidence: 74%

The morphologic spectrum of germline‐mutated BAP1‐inactivated melanocytic tumors includes lesions with conventional nevic melanocytes: A case report and review of literature

Wysozan

Khelifa

Turchan³

et al. 2019

J Cutan Pathol

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Germline mutations in BRCA1-associated protein 1 (BAP1) are associated with several neoplasms, including BAP1-inactivated melanocytic tumors (BIMTs). BIMTs are classically described as biphenotypic melanocytic proliferations with BAP1-deficient large epithelioid and rhabdoid melanocytes showing various degrees of cytologic atypia. This morphology has been traditionally classified as "spitzoid" despite the various differences between these lesions and the more classic Spitz nevi. Herein, we report a case of an otherwise healthy 11-year-old female patient with a family history of several malignancies who presented with multiple pink to brown papules. Histologic and immunohistochemical evaluation identified three lesions with loss of nuclear BAP1 staining. The histologic spectrum of these lesions included junctional spitzoid cells within a triphenotypic proliferation and a separate lesion composed entirely of dermal small to medium-sized epithelioid melanocytes with maturation.BAP1 gene sequencing revealed a germline frameshift pathogenic BAP1 mutation, denoted c.1717delC. This case provides further evidence that not all BIMTs conform to classic morphological criteria and that the morphologic spectrum includes lesions resembling conventional nevi. As BIMTs can serve as an early marker of the BAP1 hereditary tumor predisposition syndrome, we believe a need exists for a more comprehensive combined clinical and pathological approach for BIMT identification. K E Y W O R D S BAP1-inactivated tumors (BIMTs), melanocytic, BRCA1 associated protein 1 (BAP1), melanocytic, Spitz

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Nuclear BAP1 loss is common in intrahepatic cholangiocarcinoma and a subtype of hepatocellular carcinoma but rare in pancreatic ductal adenocarcinoma

Cited by 20 publications

References 40 publications

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

Anatomical, histomorphological and molecular classification of cholangiocarcinoma

The morphologic spectrum of germline‐mutated BAP1‐inactivated melanocytic tumors includes lesions with conventional nevic melanocytes: A case report and review of literature

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