Establishing a Clinic-Based Pancreatic Cancer and Periampullary Tumour Research Registry in Quebec

Al, Smith; Bascuñana, Claire; Hall, Anita; Salman, Ayat; Az, Andrei; Volenik, Alexandra; Rothenmund, Heidi; Ferland, Diane; D, Lamoussenery; As, Kamath; Amre, Ramila; Çağlar, Derin; Zh, Gao; Dg, Haegert; Kanber, Yonca; Rp, Michel; Omeroglu-Altinel, Gulbeyaz; Asselah, Jamil; Bouganim, Nathaniel; Kavan, Petr; Arena, Goffredo; Barkun, Jeffrey; Chaudhury, Prosanto; Gallinger, Steven; Foulkes, William D.; Ömeroğlu, Atilla; Metrakos, Peter; Zogopoulos, George

doi:10.3747/co.22.2300

Cited by 12 publications

(12 citation statements)

References 45 publications

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“…14, 51 The Fanconi Anemia genes, FANCG and FANCL , are also noteworthy since HDR genes are of particular interest in PC. 18-21 A nonsynonymous variant previously associated with Fanconi Anemia in FANCG has been previously described in a cell line derived from an early onset PC and demonstrated LOH. 52 However only intronic variants were observed in a follow up study of 38 familial PC kindreds.…”

Section: Discussionmentioning

confidence: 98%

“…PC cases enrolled in the Ontario 20 or Quebec 21 Pancreas Cancer Studies (OPCS, QPCS) were selected for WES of lymphocyte or white blood cell (surrogate germline) DNA. This series of cases (discovery set) included 8 young onset cases (diagnosed at 50 years of age or less) and 101 cases from 85 families with two or more PC-affected relatives (Table S1).…”

Section: Methodsmentioning

confidence: 99%

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Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer

et al. 2016

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The genetic basis underlying the majority of hereditary pancreatic adenocarcinoma (PC) is unknown. Since DNA repair genes are widely implicated in gastrointestinal malignancies, including PC, we hypothesized that there are novel DNA repair PC susceptibility genes. As germline DNA repair gene mutations may lead to PC subtypes with selective therapeutic responses, we also hypothesized that there is an overall survival (OS) difference in mutation carriers versus non-carriers. We therefore interrogated the germline exomes of 109 high-risk PC cases for rare protein-truncating variants (PTVs) in 513 putative DNA repair genes. We identified PTVs in 41 novel genes among 36 kindred. Additional genetic evidence for causality was obtained for 17 genes, with FAN1, NEK1 and RHNO1 emerging as the strongest candidates. An OS difference was observed for carriers versus non-carriers of PTVs with early stage (≤ IIB) disease. This adverse survival trend in carriers with early stage disease was also observed in an independent series of 130 PC cases. We identified candidate DNA repair PC susceptibility genes and suggest that carriers of a germline PTV in a DNA repair gene with early stage disease have worse survival.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer

et al. 2016

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“…Clinical information was obtained upon the original pathology requisitions and physician's notes in the charts. The study was approved by the institutional Research Ethics Board (REB) [40]. …”

Section: Methodsmentioning

confidence: 99%

Reg proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in pancreatic ductal adenocarcinoma

Wang

Zogopoulos

et al. 2016

Oncotarget

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry. In the 3-dimensional culture of mouse acinar cells, Reg3A promoted ADM formation with concurrent activation of mitogen-acitvated protein kinase. Upregulation of Reg1A and Reg1B levels was observed as benign ductal epithelium progresses from PanIN to invasive PDAC. Patients with PDAC showed significantly higher serum levels of Reg1A and Reg1B than matching healthy subjects. These results were further validated by the quantification of Reg 1A and 1B mRNA levels in the microdissected tissues (22- and 6-fold increases vs. non-tumor tissues). Interestingly, patients with higher levels of Reg1A and 1B exhibited improved survival rate than those with lower levels. Furthermore, tissue expressions of Reg1A, Reg1B, and Reg4 could differentiate metastatic PDAC in the liver from intrahepatic cholangiocarcinoma with 92% sensitivity and 95% specificity. Overall, our results demonstrate the upregulation of Reg proteins during PDAC development. If validated in larger scale, Reg1A and Reg1B could become clinical markers for detecting early stages of PDAC, monitoring therapeutic response, and/or predicting patient's prognosis.

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“…The PC cases were collected from two individual case series, consisting of patients enrolled in either the Quebec Pancreas Cancer Study (QPCS) or the Ontario Pancreas Cancer Study (OPCS) [12,13].…”

Section: Methodsmentioning

confidence: 99%

A region-based gene association study combined with a leave-one-out sensitivity analysis identifies SMG1 as a pancreatic cancer susceptibility gene

et al. 2019

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Pancreatic adenocarcinoma (PC) is a lethal malignancy that is familial or associated with genetic syndromes in 10% of cases. Gene-based surveillance strategies for at-risk individuals may improve clinical outcomes. However, familial PC (FPC) is plagued by genetic heterogeneity and the genetic basis for the majority of FPC remains elusive, hampering the development of gene-based surveillance programs. The study was powered to identify genes with a cumulative pathogenic variant prevalence of at least 3%, which includes the most prevalent PC susceptibility gene, BRCA2. Since the majority of known PC

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Establishing a Clinic-Based Pancreatic Cancer and Periampullary Tumour Research Registry in Quebec

Cited by 12 publications

References 45 publications

Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer

Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer

Reg proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in pancreatic ductal adenocarcinoma

A region-based gene association study combined with a leave-one-out sensitivity analysis identifies SMG1 as a pancreatic cancer susceptibility gene

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