Loss of BAP1 Leads to More YAPing in Pancreatic Cancer

Brekken, Rolf A.

doi:10.1158/0008-5472.can-20-0592

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…Mutations in the BAP1 gene commonly result in cancers and recent findings indicate that germline BAP1 mutations cause Ivyspring International Publisher a hereditary cancer syndrome with increased risk of mesothelioma and uveal melanoma. In addition, somatic BAP1 mutations are frequent in various human cancers, including uveal melanoma and mesothelioma, and have been noted in breast, lung, and renal cancers [6], but have not previously been appreciated as a significant somatic alteration in HCC.…”

Section: Journal Of Cancermentioning

confidence: 99%

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Yan¹,

Meng²,

Ding³

et al. 2022

J. Cancer

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BRCA1-Associated Protein 1 (BAP1) is a deubiquitylase that is found associated with multiprotein complexes that regulate key cellular pathways, and subsequent researches have revealed that BAP1 acts independently as a tumor suppressor. Somatic BAP1 mutations occur in various malignancies, but malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. Whether somatic mutation or expression alteration of BAP1 in hepatocellular carcinoma (HCC) influence carcinogenesis or immunogenicity is still unknown. In this study, we analyzed RNA expression, immune infiltration, survival and mutation data of HCC from The Cancer Genome Atlas databases. The association between BAP1 and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high BAP1 expression was significantly worse than that of patients with low BAP1 expression, and multivariate analyses revealed that BAP1 expression was an independent prognostic factor for poor prognosis. HCC with high BAP1 expression was associated with low ESTIMATE Score, recruitment of more tumor-infiltrating macrophage, and elevated levels of tumor mutation burden, microsatellite instability, neoantigen count, as well as programmed death-ligand1 in HCC. In addition, BAP1 mutated HCC showed reduced ability to promote ferroptosis and high BAP1 expression was correlated with ferroptosis. In conclusion, high BAP1 expression reflects immunosuppression and ferroptosis in HCC. BAP1 is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive ferroptosis-promoting therapy or immunotherapy.

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Section: Journal Of Cancermentioning

confidence: 99%

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Yan¹,

Meng²,

Ding³

et al. 2022

J. Cancer

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“…35,36 BAP1 can be lost in other tumors, including melanoma, mesothelioma, prostatic adenocarcinoma, renal cell carcinomas, pancreatic adenocarcinoma, lung adenocarcinoma, gastroesophageal cancers, cervical gastric-type adenocarcinoma, and even HCCs. [37][38][39][40][41][42][43] Therefore, BAP1 loss is neither sensitive nor specific for diagnosing iCCA. Molecular alterations have also been used to differentiate HCC from iCCA.…”

Section: Discussionmentioning

confidence: 99%

HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas

Patil

Taddei

Jain

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Intrahepatic cholangiocarcinoma (iCCA) needs to be distinguished from hepatocellular carcinoma (HCC) and metastasis, and in the absence of any specific biliary markers, is often a diagnosis of exclusion. Hepatocyte nuclear factor (HNF)-1β is a transcription factor that plays a critical role in bile duct system morphogenesis. Objective.— To investigate the diagnostic value of HNF-1β to differentiate iCCA from HCC by immunohistochemistry and compare HNF-1β with C-reactive protein (CRP), a previously identified marker for iCCA. Design.— Cases of iCCA (n = 75), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) (n = 13) and HCC (n = 65) were included in the study. Results.— All cases of iCCA (74 of 74, 100%) expressed HNF-1β compared with CRP expressed in 72.60% (53 of 73). The sensitivity and specificity of HNF-1β to differentiate iCCA from HCC was 100% and 92.31%, whereas the sensitivity and specificity for CRP was 75.58% and 7.79%. The expression of HNF-1β was greater in iCCA and the CCA component of cHCC-CCA compared with CRP (87 of 87, 100% versus 65 of 86, 75.58%, P < .001). On the contrary, CRP was more frequently expressed compared with HNF-1β in HCC and HCC component of cHCC-CCA (71 of 77, 92.21% versus 6 of 78, 7.69%; P < .001). Conclusions.— Our data indicate that HNF-1β is a more sensitive and specific marker than CRP for the diagnosis of iCCA and to identify the CCA component in cHCC-CCA. Lack of HNF-1β expression may be used to exclude iCCA from consideration in cases of adenocarcinomas of unknown primary.

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“…So far, PIK3CA mutations initiating tumorigenesis of PC have only been observed in mice, and the role it has in human PC oncogenesis needs to be explored[ 19 ]. The BAP1 gene encodes BRCA1-associated protein 1, which suppresses tumors by promoting the activity of the Hippo tumor suppressor pathway[ 20 ]. Therefore, BAP1- inactivating mutations contribute to tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Long-term survival of a patient with pancreatic cancer and lung metastasis: A case report and review of literature

Yang¹,

Yang²,

Lu³

et al. 2021

WJCC

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BACKGROUND Pancreatic cancer (PC) is a leading cause of cancer-related death, given its poor prognosis and the limited benefits of traditional therapies. As tumors become more genetically disorganized as they progress, genetic mutations might become new markers for us to predict their behavior. Nowadays, many inhibitors can selectively target gene products as a form of targeted therapy, with some showing promise as treatment for various types of cancer. CASE SUMMARY We describe a rare case of a PC patient with long-term survival of more than 8 yr. The patient was diagnosed with pancreatic ductal adenocarcinoma (PDAC) with BAP1 and PIK3CA gene mutations and Raf1 fusion and achieved partial response twice after treatment with apatinib in combination with chemotherapy. CONCLUSION BAP1, PIK3CA mutations, and Raf1 fusion are rare in PDAC. Patients with these three gene alterations of PDAC may achieve long-term survival with apatinib. Further research in other contexts is needed to determine whether apatinib has ideal efficacy for PC treatment.

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Loss of BAP1 Leads to More YAPing in Pancreatic Cancer

Cited by 5 publications

References 10 publications

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas

Long-term survival of a patient with pancreatic cancer and lung metastasis: A case report and review of literature

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