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pancreatic cancer molecular classification

Maarten F Bijlsma, Anguraj Sadanandam, Patrick Tan, Louis Vermeulen
Malignancies of the gastrointestinal tract are among the most common human cancers. The distinct tissues of origin give rise to a diverse set of diseases, such as colorectal cancer, pancreatic carcinoma and gastric cancers, with each associating with specific clinical features. Genomic and transcriptomic analyses have further defined the heterogeneity that occurs within these cancers by identifying so-called molecular subtypes. These subtypes are characterized by specific genetic aberrations and expression signatures that suggest important biological differences...
April 12, 2017: Nature Reviews. Gastroenterology & Hepatology
Yongxing Du, Bangbo Zhao, Ziwen Liu, Xiaoxia Ren, Wenjing Zhao, Zongze Li, Lei You, Yupei Zhao
Pancreatic cancer remains one of the most lethal malignancies, and insights into both personalized diagnosis and intervention of this disease are urgently needed. The rapid development of sequencing technologies has enabled the successive completion of a series of genetic and epigenetic sequencing studies of pancreatic cancer. The mutational landscape of pancreatic cancer is generally portrayed in terms of somatic mutations, structural variations, epigenetic alterations and the core signaling pathways. In recent years, four significant molecular subtype classifications of pancreatic cancer have been proposed based on the expression of transcription factors and downstream targets or the distribution of structural rearrangements...
2017: Journal of Cancer
Huan-Jun Liu, Yuan-Ying Guo, Du-Jun Li
AIM: The use of saliva as a diagnostic fluid enables non-invasive sampling and thus is a prospective sample for disease tests. This study fully utilized the information from the salivary transcriptome to characterize pancreatic cancer related genes and predict novel salivary biomarkers. METHODS: We calculated the enrichment scores of gene ontology (GO) and pathways annotated in Kyoto Encyclopedia of Genes and Genomes database (KEGG) for pancreatic cancer-related genes...
September 22, 2016: Pathology, Research and Practice
Akihiro Ohmoto, Hirofumi Rokutan, Shinichi Yachida
Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data...
January 13, 2017: International Journal of Molecular Sciences
Matthew W Rosenbaum, Martin Jones, Jonathan C Dudley, Long P Le, A John Iafrate, Martha B Pitman
BACKGROUND: The diagnosis of a pancreatic cyst as mucinous or high-risk dictates the need for follow-up or surgery. Molecular analysis of aspirated pancreatic cyst fluid (PCF) can provide valuable information not obtained by carcinoembryonic antigen (CEA) analysis or cytology. METHODS: All patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow-up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next-generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy...
January 2017: Cancer
Chantal Dreyer, Pauline Afchain, Isabelle Trouilloud, Thierry André
This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion)...
July 2016: Bulletin du Cancer
Samantha Kaufhold, Hermes Garbán, Benjamin Bonavida
The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG's expressions and activities...
May 25, 2016: Journal of Experimental & Clinical Cancer Research: CR
Haoqiang Ying, Prasenjit Dey, Wantong Yao, Alec C Kimmelman, Giulio F Draetta, Anirban Maitra, Ronald A DePinho
With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses...
February 15, 2016: Genes & Development
Markus A Schirmer, Claudia M Lüske, Sebastian Roppel, Alexander Schaudinn, Christian Zimmer, Ruben Pflüger, Martin Haubrock, Jacobe Rapp, Cenap Güngör, Maximilian Bockhorn, Thilo Hackert, Thomas Hank, Oliver Strobel, Jens Werner, Jakob R Izbicki, Steven A Johnsen, Jochen Gaedcke, Jürgen Brockmöller, B Michael Ghadimi
BACKGROUND: A genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects. METHODS: This study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy...
May 2016: Journal of the National Cancer Institute
Yihuan Luo, Xin Zhang, Zhong Tan, Peirong Wu, Xuelian Xiang, Yiwu Dang, Gang Chen
BACKGROUND: There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients...
2015: PloS One
Filippos Kottakis, Nabeel Bardeesy
Pancreatic cancers consist of a heterogeneous amalgam of assorted cell types, making it challenging to develop a classification system that groups these tumors according to common molecular features. A new study tackles this important issue using bioinformatics approaches to decipher gene expression signatures derived specifically from either tumor cells or nonmalignant stromal cells that predict patient outcome and may inform personalized treatments.
October 2015: Nature Genetics
Simona Gurzu, Sabin Turdean, Attila Kovecsi, Anca Otilia Contac, Ioan Jung
Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET)...
May 16, 2015: World Journal of Clinical Cases
P A Schnabel, K Junker
CLASSIFICATION: In the recently published 4th edition of the World Health Organization (WHO) classification of tumors of the lungs, pleura, thymus and heart, all neuroendocrine tumors of the lungs (pNET) are presented for the first time in one single chapter following adenocarcinoma and squamous cell carcinoma and before large cell carcinoma. In this classification, high grade small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are differentiated from intermediate grade atypical carcinoids (AC) and low grade typical carcinoids as well as from preinvasive lesions (DIPNECH)...
May 2015: Der Pathologe
Tobias S Schiergens, Simone Reu, Jens Neumann, Bernhard W Renz, Hanno Niess, Stefan Boeck, Volker Heinemann, Christiane J Bruns, Karl-Walter Jauch, Axel Kleespies
BACKGROUND: The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). METHODS: Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study...
July 2015: Surgery
J Yang, Y Zeng
OBJECTIVE: Pancreatic cancer is one of the most lethal diseases, and the pathogenesis remains largely unknown. To this end, we performed an integrated analysis of miRNA and mRNA expression data to explore the deregulation of miRNA and mRNA and regulatory processes underlying pancreatic cancer. MATERIALS AND METHODS: We combined mRNA and miRNA expression data with miRNA target predictions to infer new miRNA regulation activities in pancreatic cancer. We first integrated miRNA and mRNA expression profiling separately to identify differently expressed miRNA and mRNA in pancreatic cancer...
2015: European Review for Medical and Pharmacological Sciences
Huiyuan Tang, Sudhir Singh, Katie Partyka, Doron Kletter, Peter Hsueh, Jessica Yadav, Elliot Ensink, Marshall Bern, Galen Hostetter, Douglas Hartman, Ying Huang, Randall E Brand, Brian B Haab
The sialyl-Lewis A (sLeA) glycan forms the basis of the CA19-9 assay and is the current best biomarker for pancreatic cancer, but because it is not elevated in ∼25% of pancreatic cancers, it is not useful for early diagnosis. We hypothesized that sLeA-low tumors secrete glycans that are related to sLeA but not detectable by CA19-9 antibodies. We used a method called motif profiling to predict that a structural isomer of sLeA called sialyl-Lewis X (sLeX) is elevated in the plasma of some sLeA-low cancers. We corroborated this prediction in a set of 48 plasma samples and in a blinded set of 200 samples...
May 2015: Molecular & Cellular Proteomics: MCP
Arvind Rishi, Michael Goggins, Laura D Wood, Ralph H Hruban
Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives...
February 2015: Seminars in Oncology
C Huang, W Yu, Q Wang, H Cui, Y Wang, L Zhang, F Han, T Huang
AIM: Long non-coding RNA PVT1 (lncRNA PVT1) has been identified and it plays an oncogenic role in various human cancers. However, its roles in pancreatic cancer remain unclear. The aim of this paper was to explore the PVT1 expression levels and relationship with survival of patients with pancreatic ductal adenocarcinoma (PDAC) and to establish the significance of PVT1 in the development and progression of PDAC. METHODS: In this study, quantitative real-time polymerase chain reaction was performed to analyze the expression levels of lncRNA PVT1 in paired PDAC and adjacent nontumor tissues...
June 2015: Minerva Medica
Hanno Matthaei, Alexander Semaan, Ralph H Hruban
Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This understanding, when integrated with meticulous histologic analyses and with clinical findings, has direct clinical implications. The recent sequencing of all of the major types of cystic and noncystic neoplasms of the pancreas has revealed opportunities for molecular diagnoses and for personalized treatment...
May 2015: Journal of Gastroenterology
Irene Esposito, Björn Konukiewitz, Anna Melissa Schlitter, Günter Klöppel
Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection...
October 14, 2014: World Journal of Gastroenterology: WJG
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