Understanding pancreatic cancer genomes

Cowley, Mark J.; Chang, David K.; Johns, Amber; Waddell, Nicola; Grimmond, Sean M.; Biankin, Andrew V.

doi:10.1007/s00534-013-0610-6

Cited by 31 publications

(20 citation statements)

References 23 publications

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“…11 Genetic and Molecular Aberrations in PC The Australian Pancreatic Genome Initiative (APGI) sequenced the genome, epigenome, and transcriptome of 350 PCs as part of the International Cancer Genome Consortium initiative to catalogue the genomic aberrancies of 50 different cancer types. 12 As a result of the APGI work, it is evident that PCs have a diverse array of histologically indistinguishable molecular and genetic aberrations. 13,14 These include activation of the K-ras oncogene, inactivation of the tumor suppressor gene CDNK2A, and mutation or inactivation of the tumor suppressor genes TP53 and SMAD4.…”

Section: Pancreatic Cancermentioning

confidence: 99%

“…Almost all PCs have 1 or 4 of these mutations, but there are a host of other mutations such as TTN and other lower incidence (<10%) mutations that account for the heterogeneity of PCs. 12,13 The most frequent mutations are K-ras (95%), TP53 (33%), and SMAD4 (16%). 13 Pancreatic cancer also has an intense desmoplastic stroma that dilutes the mutational signal from the primary tumor, which has to be overcome in identifying tumor mutations.…”

Section: Pancreatic Cancermentioning

confidence: 99%

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Advances in Molecular Pathology and Treatment of Periampullary Cancers

Chandrasegaram¹,

Chen

Price

et al. 2016

Pancreas

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Section: Pancreatic Cancermentioning

confidence: 99%

Section: Pancreatic Cancermentioning

confidence: 99%

Advances in Molecular Pathology and Treatment of Periampullary Cancers

Chandrasegaram¹,

Chen

Price

et al. 2016

Pancreas

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“…Apart from conventional chemotherapy, targeted therapeutic approaches have not been proven to produce robust clinical outcomes in PDAC patients except for erlotinib, which is the first approved targeted therapy that selectively inhibits the EGFR tyrosine kinase (Kang and Saif, 2008;Moore et al, 2007). This is also caused by the fact that asymptomatic and/ or subclinical disease states, together with the wide variety of clinical subtypes, are characterized by inter-and intraindividual genotypic and phenotypic heterogeneity that commonly delays an accurate clinical diagnosis (Biankin et al, 2012;Cowley et al, 2013;Jones et al, 2008).…”

mentioning

confidence: 99%

Study of Clinical Survival and Gene Expression in a Sample of Pancreatic Ductal Adenocarcinoma by Parsimony Phylogenetic Analysis

Nalbantoglu

Abu‐Asab

Tan

et al. 2016

OMICS: A Journal of Integrative Biology

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Pancreatic ductal adenocarcinoma (PDAC) is one of the rapidly growing forms of pancreatic cancer with a poor prognosis and less than 5% 5-year survival rate. In this study, we characterized the genetic signatures and signaling pathways related to survival from PDAC, using a parsimony phylogenetic algorithm. We applied the parsimony phylogenetic algorithm to analyze the publicly available whole-genome in silico array analysis of a gene expression data set in 25 early-stage human PDAC specimens. We explain here that the parsimony phylogenetics is an evolutionary analytical method that offers important promise to uncover clonal (driver) and nonclonal (passenger) aberrations in complex diseases. In our analysis, parsimony and statistical analyses did not identify significant correlations between survival times and gene expression values. Thus, the survival rankings did not appear to be significantly different between patients for any specific gene ( p > 0.05). Also, we did not find correlation between gene expression data and tumor stage in the present data set. While the present analysis was unable to identify in this relatively small sample of patients a molecular signature associated with pancreatic cancer prognosis, we suggest that future research and analyses with the parsimony phylogenetic algorithm in larger patient samples are worthwhile, given the devastating nature of pancreatic cancer and its early diagnosis, and the need for novel data analytic approaches. The future research practices might want to place greater emphasis on phylogenetics as one of the analytical paradigms, as our findings presented here are on the cusp of this shift, especially in the current era of Big Data and innovation policies advocating for greater data sharing and reanalysis.

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“…Significant effort has recently been made to examine PDAC at genomic, transcriptomic, and proteomic levels, aiming to identify screening, diagnostic, prognostic, and predictive biomarkers for PDAC [3][4][5][6][7][8][9][10]. Despite this, many questions concerning the molecular pathology of PDAC still remain unanswered [4,5,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Despite this, many questions concerning the molecular pathology of PDAC still remain unanswered [4,5,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein status as well as expression of epithelial-to-mesenchymal transition markers and cell cycle regulators at the stage of liver metastasis

Liszka¹

2014

pjp

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There are limited data on the biology of metastatic pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to compare the expression of immunohistochemical markers that may be involved in the development of metastatic disease in primary PDAC and in synchronous liver metastatic tissues. Thirty-two stains (corresponding to proteins encoded by 31 genes: SMAD4, TP53, ACTA2, CDH1, CDKN1A, CLDN1, CLDN4, CLDN7, CTNNB1, EGFR, ERBB2, FN1, KRT19, MAPK1/MAPK3, MAPK14, MKI67, MMP2, MMP9, MUC1 (3 antibodies), MUC5AC, MUC6, MTOR, MYC, NES, PTGS2, RPS6, RPS6KB1, TGFB1, TGFBR1, VIM)were evaluated using tissue microarray of 26 pairs of primary PDACs and their liver metastases. There were no significant differences in expression levels of examined proteins between primary and secondary lesions. In particular, metastatic PDAC retained the primary tumour's SMAD4 protein status in all and p53 protein status in all but one case. This surprising homogeneity also involved expression levels of markers of epithelial-to-mesenchymal transition as well as cell cycle regulators studied. In conclusion, the biological profiles of primary PDACs and their liver metastases seemed to be similar. Molecular alterations of PDAC related to a set of immunohistochemical markers examined in the present study were already present at the stage of localized disease.

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Understanding pancreatic cancer genomes

Cited by 31 publications

References 23 publications

Advances in Molecular Pathology and Treatment of Periampullary Cancers

Advances in Molecular Pathology and Treatment of Periampullary Cancers

Study of Clinical Survival and Gene Expression in a Sample of Pancreatic Ductal Adenocarcinoma by Parsimony Phylogenetic Analysis

Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein status as well as expression of epithelial-to-mesenchymal transition markers and cell cycle regulators at the stage of liver metastasis

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