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Pancreatic Neoplasms: HELP
Articles by V. Bernard
Based on 4 articles published since 2010
(Why 4 articles?)
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Between 2010 and 2020, V. Bernard wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients. 2018

Castillo, J / Bernard, V / San Lucas, F A / Allenson, K / Capello, M / Kim, D U / Gascoyne, P / Mulu, F C / Stephens, B M / Huang, J / Wang, H / Momin, A A / Jacamo, R O / Katz, M / Wolff, R / Javle, M / Varadhachary, G / Wistuba, I I / Hanash, S / Maitra, A / Alvarez, H. ·Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · The University of Texas MD Anderson Cancer UTHealth Graduate School of Biomedical Sciences, Houston, USA. · Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA. · ContinuumDx, Houston, USA. · McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #29045505.

ABSTRACT: Background: Detection of circulating tumor DNA can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We carried out a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal 'surfaceome' in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling. Patients and methods: Surface exosomal proteins were profiled in 13 human PDAC and 2 non-neoplastic cell lines by liquid chromatography-mass spectrometry. A total of 173 prospectively collected blood samples from 103 PDAC patients underwent exosome isolation. Droplet digital PCR was used on 74 patients (136 total exosome samples) to determine baseline KRAS mutation call rates while patients were on therapy. PDAC-specific exosome capture was then carried out on additional 29 patients (37 samples) using an antibody cocktail directed against selected proteins, followed by droplet digital PCR analysis. Exosomal DNA in a PDAC patient resistant to therapy were profiled using a molecular barcoded, targeted sequencing panel to determine the utility of enriched nucleic acid material for comprehensive molecular analysis. Results: Proteomic analysis of the exosome 'surfaceome' revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151, LGALS3BP, HIST2H2BE, and HIST2H2BF. KRAS mutations in total exosomes were detected in 44.1% of patients undergoing active therapy compared with 73.0% following exosome capture using the selected biomarkers. Enrichment of exosomal cargo was amenable to molecular profiling, elucidating a putative mechanism of resistance to PARP inhibitor therapy in a patient harboring a BRCA2 mutation. Conclusion: Exosomes provide unique opportunities in the context of liquid biopsies for enrichment of tumor-specific material in circulation. We present a comprehensive surfaceome characterization of PDAC exosomes which allows for capture and molecular profiling of tumor-derived DNA.

2 Article High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. 2017

Allenson, K / Castillo, J / San Lucas, F A / Scelo, G / Kim, D U / Bernard, V / Davis, G / Kumar, T / Katz, M / Overman, M J / Foretova, L / Fabianova, E / Holcatova, I / Janout, V / Meric-Bernstam, F / Gascoyne, P / Wistuba, I / Varadhachary, G / Brennan, P / Hanash, S / Li, D / Maitra, A / Alvarez, H. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA. · Genetic Epidemiology Group International Agency for Research on Cancer, Lyon, France. · Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia. · Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Department of Preventive Medicine, Palacky University of Medicine, Olomouc, Czech Republic. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. · Department of Investigational Cancer Therapeutics and the Institute for Personalized Cancer Therapy, Houston, USA. · Section of Experimental Pathology, University of Texas M.D. Anderson Cancer Center, Houston, USA · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #28104621.

ABSTRACT: Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

3 Article Minimally invasive genomic and transcriptomic profiling of visceral cancers by next-generation sequencing of circulating exosomes. 2016

San Lucas, F A / Allenson, K / Bernard, V / Castillo, J / Kim, D U / Ellis, K / Ehli, E A / Davies, G E / Petersen, J L / Li, D / Wolff, R / Katz, M / Varadhachary, G / Wistuba, I / Maitra, A / Alvarez, H. ·Department of Translational Molecular Pathology Department of Pathology. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston. · Department of Pathology The University of Texas Graduate School of Biomedical Sciences at Houston, Houston. · Department of Pathology. · Avera Institute for Human Genetics, Sioux Falls. · Department of Gastrointestinal (GI) Medical Oncology. · Department of Translational Molecular Pathology. · Department of Translational Molecular Pathology Department of Pathology Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA amaitra@mdanderson.org. ·Ann Oncol · Pubmed #26681674.

ABSTRACT: BACKGROUND: The ability to perform comprehensive profiling of cancers at high resolution is essential for precision medicine. Liquid biopsies using shed exosomes provide high-quality nucleic acids to obtain molecular characterization, which may be especially useful for visceral cancers that are not amenable to routine biopsies. PATIENTS AND METHODS: We isolated shed exosomes in biofluids from three patients with pancreaticobiliary cancers (two pancreatic, one ampullary). We performed comprehensive profiling of exoDNA and exoRNA by whole genome, exome and transcriptome sequencing using the Illumina HiSeq 2500 sequencer. We assessed the feasibility of calling copy number events, detecting mutational signatures and identifying potentially actionable mutations in exoDNA sequencing data, as well as expressed point mutations and gene fusions in exoRNA sequencing data. RESULTS: Whole-exome sequencing resulted in 95%-99% of the target regions covered at a mean depth of 133-490×. Genome-wide copy number profiles, and high estimates of tumor fractions (ranging from 56% to 82%), suggest robust representation of the tumor DNA within the shed exosomal compartment. Multiple actionable mutations, including alterations in NOTCH1 and BRCA2, were found in patient exoDNA samples. Further, RNA sequencing of shed exosomes identified the presence of expressed fusion genes, representing an avenue for elucidation of tumor neoantigens. CONCLUSIONS: We have demonstrated high-resolution profiling of the genomic and transcriptomic landscapes of visceral cancers. A wide range of cancer-derived biomarkers could be detected within the nucleic acid cargo of shed exosomes, including copy number profiles, point mutations, insertions, deletions, gene fusions and mutational signatures. Liquid biopsies using shed exosomes has the potential to be used as a clinical tool for cancer diagnosis, therapeutic stratification and treatment monitoring, precluding the need for direct tumor sampling.

4 Article Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine needle aspiration: high reproducibility and inter-observer agreement of the Ki-67 labelling index. 2014

Weynand, B / Borbath, I / Bernard, V / Sempoux, C / Gigot, J-F / Hubert, C / Lannoy, V / Deprez, P H / Jouret-Mourin, A. ·Department of Pathology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium. ·Cytopathology · Pubmed #24750272.

ABSTRACT: OBJECTIVES: Assessment of proliferation by the Ki-67 labelling index (Ki67-LI) is an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on resection specimens. Ki67-LI values for grading are not fully established on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to determine the accuracy of Ki67-LI on EUS-FNA to predict a final grade of pNET and to analyse the relationship between cytological grading and progression-free survival (PFS). METHODS: Between 1996 and 2010, 46 pNETs (33 were resected) from 45 patients were diagnosed by EUS-FNA. Ki67-LI was evaluated on cytological and histological material for each tumour and classified according to the 2010 WHO grading system. RESULTS: A very good inter-observer agreement for Ki67-LI on EUS-FNA and surgical specimens, respectively, were obtained. Discrepancies were observed between histology and cytology, especially in grade 2 (G2) tumours, where cytology underestimated grading owing to tumour heterogeneity. Still, EUS-FNA was able to distinguish a poor prognostic group, as the actuarial PFS of cytological (c) G3 tumours was 10 ± 4 months versus 29 ± 7 and 68 ± 10 for cG2 and cG1 tumours, respectively (P < 0.0001). CONCLUSION: This study attests the reproducibility of Ki67-LI of pNETs whether counted on cytology or histology with a very good inter-observer correlation. Determination of Ki67-LI on EUS-FNA of pNETs should be included systematically in their prognostic work-up.