Mutational landscape of intrahepatic cholangiocarcinoma

Zou, Sheng; Li, Jiarui; Zhou, Hai-Hua; Frech, Christian; Jiang, Xiaolan; Chu, Jeffrey Shih-Chieh; Zhao, Xinyin; Li, Yuqiong; Li, Qiaomei; Wang, Hui; Hu, Jingyi; Kong, Guanyi; Wu, Mengchao; Ding, Chuanfan; Chen, Nansheng; Hu, He-Ping

doi:10.1038/ncomms6696

Cited by 335 publications

(358 citation statements)

References 66 publications

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“…The genomic heterogeneity of CCA (TABLE 1) is not only related to the diverse anatomical location of the tumour (that is, intrahepatic, perihilar or distal) but also to the various risk factors and associated pathologies 29,[67][68][69][70][71][72][73][74][75] . The most prevalent genetic alterations identified in CCA affect key networks such as DNA repair (TP53) 72,73,75 , the WNT-CTNNB1 pathway 67 , tyrosine kinase signalling (KRAS, BRAF, SMAD4 and FGFR2) 29,68,70,[73][74][75] , protein tyrosine phosphatase (PTPN3) 71 , epigenetic (IDH1 and IDH2) 69,70,72,74,75 and chromatin-remodelling factors (histone-lysine N-methyltransferase 2C, also known as MLL3) 73 , including the SWI/SNF complex (ARID1A, PBRM1 and BAP1) 69,70,72,75 and deregulated Notch signalling, which is a key component in cholangiocyte differentiation and biliary duct development.…”

Section: Genomic Heterogeneitymentioning

confidence: 99%

“…The most prevalent genetic alterations identified in CCA affect key networks such as DNA repair (TP53) 72,73,75 , the WNT-CTNNB1 pathway 67 , tyrosine kinase signalling (KRAS, BRAF, SMAD4 and FGFR2) 29,68,70,[73][74][75] , protein tyrosine phosphatase (PTPN3) 71 , epigenetic (IDH1 and IDH2) 69,70,72,74,75 and chromatin-remodelling factors (histone-lysine N-methyltransferase 2C, also known as MLL3) 73 , including the SWI/SNF complex (ARID1A, PBRM1 and BAP1) 69,70,72,75 and deregulated Notch signalling, which is a key component in cholangiocyte differentiation and biliary duct development. Recurrent genetic variants have also been identified in the promoter of the human telomerase reverse transcriptase (TERT) 70 , which for CCA is found to be associated with chronic hepatitis 70 .…”

Section: Genomic Heterogeneitymentioning

confidence: 99%

See 1 more Smart Citation

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,058

1,139

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Section: Genomic Heterogeneitymentioning

confidence: 99%

Section: Genomic Heterogeneitymentioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,058

1,139

View full text Add to dashboard Cite

“…• Source Z2 = [56] • Source T7 = TCGA (see Acknowledgments (main text)). Sample IDs are of the form TCGA-*, where * is: 3X-AAV9, 3X-AAVA, 3X-AAVB, 3X-AAVC, 3X-AAVE, 4G-AAZO, 4G-AAZT, W5-AA2G, W5-AA2H, W5-AA2I, W5-AA2O, W5-AA2Q, W5-AA2R, W5-AA2T, W5-AA2U, W5-AA2W, W5-AA2X, W5-AA2Z, W5-AA30, W5-AA31, W5-AA33, W5-AA34, W5-AA36, W5-AA38, W5-AA39, W6-AA0S, WD-A7RX, YR-A95A, ZD-A8I3, ZH-A8Y1, ZH-A8Y2, ZH-A8Y4, ZH-A8Y5, ZH-A8Y6, ZH-A8Y8, ZU-A8S4.…”

Section: Cholangiocarcinoma (139 Samples)mentioning

confidence: 99%

Mutation Clusters from Cancer Exome

Kakushadze¹,

2017

SSRN Journal

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Abstract:We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in-and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method. Extracting stable mutation structures from exome data could have important implications for speed and cost, which are critical for early-stage cancer diagnostics, such as novel blood-test methods currently in development.

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“…Of note, the global incidence of ICC has been steadily increasing over the last 30 years (4). From the early 1970s to 1999, the ICC incidence in United States and China increased by >150% (4,5). Due to a lack of clinical symptoms and appropriate markers for early diagnosis, ICC is usually diagnosed at an advanced stage (4), mostly with local invasion, liver parenchymal and lymph node metastases, leading to a poor outcome following surgical removal, which is currently the only curative option (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…ICC is the second most frequent intrahepatic primary liver tumour after hepatocellular carcinoma (3), accounting for 5-10% of primary liver cancer cases (4). Of note, the global incidence of ICC has been steadily increasing over the last 30 years (4).…”

Section: Introductionmentioning

confidence: 99%

Glasgow Prognostic Score predicts prognosis of intrahepatic cholangiocarcinoma

Qin

Zhang

et al. 2017

Molecular and Clinical Oncology

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Abstract. High Glasgow Prognostic Score (GPS) has been associated with poor prognosis in patients with lung, ovarian, colorectal and renal cancer, as well as hepatocellular carcinoma. The aim of this study was to investigate the prognostic value of GPS in patients with intrahepatic cholangiocarcinoma (ICC) undergoing partial hepatectomy. A total of 72 patients with pathologically confirmed ICC were classified according to their GPS scores assigned based on the preoperative levels of C-reactive protein (CRP) and albumin. Their clinicopathological data were retrospectively assessed using univariate and multivariate analysis to determine their association with overall survival and recurrence. High GPS scores in ICC patients were associated with preoperative levels of CRP (P<0.001) and albumin (P<0.001), frequency of ascites accumulation (P=0.035), lymph node metastasis (P=0.002) and tumour size (P=0.005). On univariate analysis, preoperative levels of CRP (P<0.001), albumin (P=0.016) and carbohydrate antigen 19-9 (P=0.038), hepatitis B virus (HBV) positivity (P=0.009), occurrence of lymph node metastasis (P=0.001), Child-Pugh class B (P=0.013) and high tumour-node-metastasis (TNM) stage (P=0.002) were found to be associated with the 1-and 3-year overall survival. Multivariate analysis suggested that GPS score (HR=2.037, 95% CI: 1.092-3.799, P=0.025), TNM classification (HR=2.000, 95% CI: 1.188-3.367, P=0.009) and HBV positivity (HR=0.559 95% CI: 0.328-0.953, P=0.032) were independently associated with patient survival. High GPS scores also predicted ICC recurrence. In conclusion, our results demonstrated that GPS may serve as an independent marker of prognosis in patients with ICC following partial hepatectomy.

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Mutational landscape of intrahepatic cholangiocarcinoma

Cited by 335 publications

References 66 publications

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Mutation Clusters from Cancer Exome

Glasgow Prognostic Score predicts prognosis of intrahepatic cholangiocarcinoma

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