- Miriam Marqués
- Elena del Pilar Andrada
- Irene Felipe
- Mark Kalisz
- Eleonora Lapi
- Sumit Paliwal
- Ana Margarita Maldonado
- Irene Millán
- Catarina Pereira
- Mónica Pérez
- Miguel Deblas
- Natalia Del Pozo
- Jaime Martínez de Villarreal
We focus on the molecular pathophysiology of pancreatic ductal adenocarcinoma (PDAC) and urothelial carcinoma (UC), with a disease-oriented approach. We use patient samples, cultured cells, and genetically modified mice, giving a similar weight to the 3 model systems. Primary observations made at either of these levels are then extended through additional work. To translate the findings, we bring this knowledge to a ‘population’ level, leveraging on information and samples from large patient cohorts.
In PDAC, a main hypothesis is that cell differentiation is a potent tumour suppressor mechanism acting early during carcinogenesis. We use the excellent genetic mouse models that are available because these processes cannot be readily studied using human samples. PDAC can originate both in pancreatic progenitors and in acinar cells. Understanding the contribution of early molecular events is crucial in order to design better strategies for early tumour detection and prevention in subjects at risk.
In UC, we focus on identifying new genes, using them for improved tumour taxonomy, characterising the mechanisms of action, and applying this knowledge for improved prediction of outcome and therapy.
- Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches(2019)
Int J Cancer 144, 1540-1549.
- Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations(2019)
Gut 68, 130-139.
- Cdk4/6-inhibition induces bladder cancer regression independently of RB1 gene status(2019)
Clin Cancer Res 25, 390-402.
- Mouse Models Shed Light on the SLIT/ROBO Pathway in Pancreatic Development and Cancer(2019)
Trends in Cancer 5, 145-148.
- CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer Independently of RB1 Status(2019)
Clin Cancer Res 25, 390-402.
- Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas(2018)
Nature 554, 533-537.
- c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis(2018)
Gut 67, 707-718.
- Genetic unrelatedness of co-occurring pancreatic adenocarcinomas and IPMNs challenges current views of clinical management(2018)
Gut 67, 1561-1563.
- Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer(2018)
Nat Commun 9, 556-.
- Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma(2018)
Clin Cancer Res 24, 5239-5249.
- CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer Independently of RB1 Status.(2018)
Clin Cancer Res (in press).
- Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups(2018)
Clin Cancer Res 24, 1586-1593.
- Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives(2018)
Int J Epidemiol 47, 473-483.
- Asthma status is associated with decreased risk of aggressive urothelial bladder cancer(2018)
Int J Cancer 42, 470-476.
- GATA6 Controls Insulin Biosynthesis and Secretion in Adult ß-Cells(2018)
Diabetes 67, 448-460.
- Mutant Kras Dosage and Chromothripsis: The Right Ingredients for a Pancreatic Cancer Catastrophe(2018)
Trends in Cancer 4, 399-401.
- European evidence-based guidelines on pancreatic cystic neoplasms(2018)
Gut 67, 789-804.
- Agnostic pathway/gene set analysis of genome-wide association data identifies novel associations for pancreatic cancer(2018)
J Natl Cancer I (in press).
- Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.(2017)
Eur Urol 72, 354-365.
- Prognostic impact of a 12-gene progression score in non-muscle invasive bladder cancer: a prospective multicenter validation study.(2017)
Eur Urol 72, 461-469.
- PIcKing on Fibroblast Growth Factor Receptors as Bladder Cancer Therapeutic Targets.(2017)
Eur Urol 17, 863-865.
- Reduced risk of pancreatic cancer associated with asthma and nasal allergies.(2017)
Gut 66, 314-322.
- GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer.(2017)
Gut 66, 1665-1676.
- A genetic roadmap of pancreatic cancer: still evolving.(2017)
Gut 66, 2170-2178.
- A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.(2017)
Ann Oncol 28, 1618-1624.
- Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts.(2017)
Elife 6, e26980-.
- FGFR3, TERT and OTX1 as a urinary biomarker combination for surveillance of patients with bladder cancer in a large prospective multicenter study(2017)
J Urology 197, 1410-1418.
- Validation of a DNA methylation-mutation urine assay to select patients with hematuria for cystoscopy.(2017)
J Urology 197, 590-595.
- BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis.(2016)
Nat Communications 7, 10153-.
- The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice.(2016)
Gut 65, 476-486.
- A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.(2016)
Nature 538, 378-382.
- Somatic mosaicism: on the road to cancer.(2016)
Nat Rev Cancer 16, 43-55.
- Mosaic loss of chromosome Y is associated with common variation near TCL1A.(2016)
Nat Genet 48, 563-568.
- Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma.(2016)
Cancer Cell 30, 27-42.
- The N-Terminal Phosphorylation of RB by p38 Bypasses Its Inactivation by CDKs and Prevents Proliferation in Cancer Cells.(2016)
Mol Cell 64, 25-36.
- Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.(2016)
Nat Communications 7, 11843-.
- The cis-regulatory switchboard of pancreatic ductal cancer.(2016)
EMBO J 35, 558-560.
- SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150.(2016)
Oncogene 35, 2991-3003.
- Somatic embryonic FGFR2 mutations in keratinocytic epidermal nevi.(2016)
J Invest Dermatol 136, 1718-1721.
- Choline Kinase Alpha (CHKa) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors.(2016)
Mol Cancer Ther 15, 323-333.
- E-cadherin downregulation sensitizes PTEN mutant cells .(2016)
Oncotarget 7, 84054-84071.
- Inflammatory-Related Genetic Variants in Non-Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment.(2016)
Cancer Epidem Biomar 25, 1144-1150.
- FGFR3, TERT and OTX1 as urinary biomarker combination for surveillance of bladder cancer patients in a large prospective multicenter study.(2016)
J Urology (in press).
- Prediction of non-muscle invasive bladder cancer outcomes assessed by innovative multimarker prognostic models.(2016)
Bmc Cancer 16, 351-.
- International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer.(2016)
Pancreatology 16, 14-27.
- Bladder Cancer Molecular Taxonomy: Summary from a Consensus Meeting.(2016)
Bladder Cancer 2, 37-47.
- c-MYC partners with BPTF in human cancer.(2016)
Molecular Cellular Oncology 3, e1152346-.
- Mnk1 is a novel acinar cell-specific kinase required for exocrine pancreatic secretion and response to pancreatitis in mice.(2015)
Gut 64, 937-947.
- Reduced risk of pancreatic cancer associated with asthma and nasal allergies.(2015)
Gut (in press).
- Intratumour Heterogeneity in Urologic Cancers: From Molecular Evidence to Clinical Implications.(2015)
Eur Urol 67, 729-737.
- NOTCH pathway inactivation promotes bladder cancer progression.(2015)
J Clin Invest 125, 824-830.
- Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.(2015)
J Natl Cancer I 107, djv223-.
- Characterization of large structural genetic mosaicism in human autosomes.(2015)
Am J Hum Genet 96, 487-497.
- Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma.(2015)
Clin Cancer Res 21, 3512-3521.
- AID-expressing epithelium is protected from oncogenic transformation by an NKG2D surveillance pathway.(2015)
EMBO Mol Med 7, 1327-1336.
- Integration Analysis of Three Omics Data Using Penalized Regression Methods: An Application to Bladder Cancer.(2015)
PLoS Genet 11, e1005689-.
- PanGen-Fam: Spanish registry of hereditary pancreatic cancer.(2015)
Eur J Cancer 51, 1911-1917.
- PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors.(2015)
Mol Carcinogen 54, 566-576.
- The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.(2015)
Bmc Genomics 16, 403-.
- Addressing the challenges of pancreatic cancer: future directions for improving outcomes.(2015)
Pancreatology 15, 8-18.
- Epidemiology of bladder cancer.(2015)
Hematol Oncol Clin N 29, 177-189.
- Framework for the Integration of Genomics, Epigenomics and Transcriptomics in Complex Diseases.(2015)
Hum Hered 79, 124-136.
- A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma.(2015)
Int J Proteomics 2015, 587250-.
- Nicotine Promotes Initiation and Progression of KRAS-Induced Pancreatic Cancer via Gata6-Dependent Dedifferentiation of Acinar Cells in Mice.(2014)
Gastroenterology 147, 1119-1133.
- Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.(2014)
Nat Genet 46, 994-1000.
- The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.(2014)
Nat Cell Biol 16, 695-707.
- Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells.(2014)
Gastroenterology 147, 882-892.
- Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study.(2014)
Gut (in press).
- Nr5a2 heterozygosity sensitises to, and cooperates with, inflammation in KRasG12V-driven pancreatic tumourigenesis.(2014)
Gut 63, 647-655.
- Telomerase reverse transcriptase promoter mutations in bladder cancer: high frequency across stages, detection in urine, and lack of association with outcome.(2014)
Eur Urol 65, 360-366.
- Inflammatory Biomarkers and Bladder Cancer Prognosis: A Systematic Review.(2014)
Eur Urol 66, 1078-1091.
- Next-generation Sequencing of Urologic Cancers: Next Is Now.(2014)
Eur Urol 66, 4-7.
- Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells.(2014)
Nat Communications 5, 3719-.
- Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A.(2014)
Carcinogenesis 35, 2670-2678.
- LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk.(2014)
Br J Cancer 110, 2123-2130.
- LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.(2014)
Epigenetics 9, 1532-1539.
- PIM kinases as potential therapeutic targets in a subset of peripheral T cell lymphoma cases.(2014)
PLoS ONE 9, e1121148-.
- Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis.(2014)
PLoS ONE 9, e89952.-.
- Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer: an international validation in primary tumours.(2014)
PLoS ONE 9, e96849-.
- Whole Genome Prediction of Bladder Cancer Risk With the Bayesian LASSO.(2014)
Genet Epidemiol 38, 467-476.
- Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.(2013)
Nat Genet 45, 1464-1469.
- Gata6 is required for complete acinar differentiation and maintenance of the exocrine pancreas in adult mice.(2013)
Gut 62, 1481-1488.
- Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer.(2013)
Cancer Res 73, 2211-2220.
- Sirtuin-1 Regulates Acinar-to-Ductal Metaplasia and Supports Cancer Cell Viability in Pancreatic Cancer.(2013)
Cancer Res 73, 2357-2367.
- Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA.(2013)
Environ Health Persp 121, 650-656.
- Phacomatosis pigmentokeratotica is caused by a postzygotic HRAS mutation in a multipotent progenitor cell.(2013)
J Invest Dermatol 133, 1998-2003.
- Bladder cancer and seroreactivity to BK, JC and Merkel cell polyomaviruses: The Spanish bladder cancer study.(2013)
Int J Cancer 133, 597-603.
- ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression in tumours.(2013)
Biochem J 451, 395-405.
- ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.(2013)
PLoS ONE 8, e62483-.
- Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk.(2013)
PLoS ONE 8, e83745-.
- EU Pancreas: An Integrated European Platform for Pancreas Cancer Research – from Basic Science to Clinical and Public Health Interventions for a Rare Disease.(2013)
Public Health Genomics 16, 305-312.
- Many mosaic mutations.(2013)
Curr Oncol 20, 85-87.