IMPPC Fundación Institut de Medicina Predictiva i Personalitzada del Càncer

 

Our group  focuses on studying the genetic predisposition of humans to develop cancer. We study individuals who inherit certain mutated genes that predispose them to develop cancer and we also study the genetics of their tumors to understand the mechanisms leading to tumor development and progression. We use the baker's yeast Saccharomyces cerevisiae to do experimental tests that we cannot perform in humans. As cancer is a complex disease, our group is interested in studying in depth the genetic architecture of complex traits, which are still unknown. We believe our findings will also be useful for understanding what is happening in individuals who develop sporadic cancers, which are more common.

We focus our scientific interests in 4 research areas:

1) Hereditary and familial cancers

We are interested in inherited diseases that predispose an individual to develop cancer and also in families in which there are different individuals affected by the same type of cancer. We are currently mainly focused in Neurofibromatosis type 1 but willing to expand to other cancer syndromes. We work together with molecular diagnostic and genetic counseling units in order to translate research into benefit for the patients. We are also interested in understanding the genetic basis of tumors and other traits associated to these diseases. Finally we are interested in understanding how other genetic factors, besides inherited mutated genes, contribute to the development of associated tumors.

2) Somatic cell genetics

The group is interested in the somatic mutation rate in humans, in the mutational mechanisms contributing to it, and in the resulting somatic genomic variation in the different tissues. We would like to understand the role of somatic mutation rate and somatic genomic variation in health and disease.

3) Yeast as an experimental model for cancer genetics

We use baker's yeast (Saccharomyces cerevisiae) to study cancer genetics in two different ways: a) To study gene-gene and gene-environment interactions in an experimentally tractable genetic model; b) To study how genomic variation affects cell physiology, centering our efforts in DNA repair mechanisms such as homologous recombination and also in prototypical signal transduction pathways involved in cancer.

4) Genetic architecture of complex traits 

Cancer is complex but added to this many aspects of cancer, such as the cellular mechanisms governing tumor development, are complex in themselves. We must therefore investigate the fundamental principles of complex traits, such as their genetic architecture, to understand how complexity in biology is determined genetically and orchestrated molecularly. To do this we study humans and also use a yeast model system.

 

 

 

 

 

 

 

 

 

 

 

 

 

Available Resources

A) Molecular karyotype and tumor LOH analysis tools
Our group is developing standard molecular tools for the rapid analysis of mechanisms leading to LOH in tumors. A microsatellite multiplex PCR analysis allow us to assess LOH, identify copy number changes, identify the mutational mechanism leading to LOH and estimate the number of cells within tumors carrying LOH.
We are also using SNP-array analysis to perform molecular karyotypes of tumors.

B) High-throughput genetic analysis in yeast

It is the intention of the group to set up in the lab the capacity for performing high-throughput genetic analysis in two different ways:

a)   Analyzing genetic interactions and genetic-environment interactions by the use of yeast deletion strain collections, and translate this information into functional information by the use of other strain collections and yeast resources.
b)   To exploit the genetic variation of distinct yeast strains, combined with genomic resources available in yeast, for better understanding fundamental aspects of complex traits.

Funding

Project Title:Número de tumores benignos como fenotipo indicador de la tasa de mutación somática in vivo: identificación de genes responsables del número de tumores asociados a la Neurofibromatosis tipo 1"
Funding body:Instituto de Salud Carlos III-Fondo de Investigación Sanitaria
Duration: From 2009 to 2011
PI: Eduard Serra Arenas

Collaborations

Dr. Conxi Lázaro
Laboratori de Recerca Translacional, Institut Català d'Oncologia-IDIBELL

Dr. Ignacio Blanco
Unitat de Consell Genètic, Institut Català d'Oncologia

Dr. Nancy Ratner and The NF1 Microarray Consortium
Divisions of Experimental Hematology and Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Dr. Hildegard Kehrer-Sawatzki
Institute of Human Genetics, University of Ulm, Germany

Dr. Eric Legius
Center of Human Genetics, Catholic University of Leuven, Belgium

Tapan Mehta
Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA

Contact: eserra(at)imppc.org

 Selected Publications:

Hereditary and Familial Cancers

Eva Pros, Juana Fernandez-Rodriguez, Belen Canet, Llúcia Benito, Aurora Sánchez, Ana Benavides, Feliciano J. Ramos, Maria Asunción López-Ariztegui, Gabriel Capellà, Ignacio Blanco, Eduard Serra,Conxi Lázaro. Antisense therapeutics for Neurofibromatosis Type 1 Caused by Deep Intronic Mutations, Human Mutation, 2009, Human Mutation 30(3): 454-62

Eva Pros, Carolina Gómez, Thamar Martín, Pere Fábregas, Eduard Serra, Conxi Lázaro. Nature and mRNA Effect of 282 Different NF1 point mutations: focus on splicing alterations. Human Mutation 29:E173-E193 (2008)

Eduard Serra, Eva Pros, Carles Garcia, Eva López, M. Lluïsa Gili, Carolina Gómez, Anna Ravella, Gabriel Capellà, Ignacio Blanco and Conxi Lázaro. Tumor LOH analysis provides reliable linkage information for prenatal genetic testing of sporadic NF1 patients. Gen Chrom & Can 46:820-827 (2007)

Pros E, Larriba S, López E, Ravella A, Gili MLL, Kruyer H, Valls J, Eduard Serra, Lázaro C. NF1 mutation rather than individual genetic variability is the main determinant of the NF1-transcriptinal profile of mutations affecting splicing. Human Mutation 27: 1104-1114 (2006)

Somatic mutation rate, mutational mechanisms and tumor development

Raedt T, Maertens O, Eduard Serra, Legius E. Somatic NF1 Mutations in Tumors and Other Tissues. Kaufmann D (ed): Neurofibromatoses. Monogr Hum Genet. Basel, Karger, 2008, vol 16, pp 143-153

Katharina Steinmann, David N. Cooper, Lan Kluwe, Nadia A. Chuzhanova, Cornelia Senger, Eduard Serra, Conxi Lazaro, Montserrat Gilaberte, Katharina Wimmer, Viktor-Felix Mautner, Hildegard Kehrer-Sawatzki. Type-2 NF1 deletions are highly unusual by virtue of the absence of non-allelic homologous recombination hotspots and an apparent preference for female mitotic recombination. American Journal of Human Genetics 81(6): 1201-1220 (2007)

Eduard Serra, T Rosenbaum, M Nadal, U Winner, E Ars, X Estivill, C Lázaro. Mitotic recombination effects homozygosity for NF1 germline mutations in neurofibromas. Nature Genetics 28:294-296 (2001)

Eduard Serra, T Rosenbaum, U Winner, R Aledo, E Ars, X Estivill, H-G Lenard, C Lázaro. Schwann cells harbor the somatic NF1 mutation in neurofibromas: evidence of two different Schwann cell subpopulations. Human Molecular Genetics 9: 3055-3064 (2000)

Yeast as a model system

Richard C. Yu, C. Gustavo Pesce, Alejandro Colman-Lerner, Larry Lock, David Pincus, Eduard Serra, Mark Holl, Kirsten Benjamin, Andrew Gordon and Roger Brent.  Negative feedback that improves information transmission in yeast, 2008, Nature 456 (7223): 755-61

RC Yu, O Resnekov, AP Abola, SS Andrews, KR Benjamin, J Bruck, IE Burbulis, A Colman-Lerner, D Endy, A. Gordon, M Holl, L Lock, CG Pesce, Eduard Serra, RD Smith, TM Thomson, AE Tsong, R Brent. The Alpha Project: a model system for systems biology research. IET Systems Biology 2(5) 222-233 (2008)

Alejandro Colman-Lerner*, Andrew Gordon, Eduard Serra, Tina Chin, Orna Resnekov, Drew Endy, Gustavo Pesce and Roger Brent. Regulated Cell to Cell Variation in a Cell Fate Decision System. Nature 437(7059): 699-706 (2005)

Group Members

Josep Biayna
Carles Garcia Linares
Jaume Mercade
Eduard Serra, Group Leader
Ernest Terribas
Elisabet Castellanos, Joint Program
Inma Rosas, Joint Program