Innovating Works

PID2020-118795GB-I00

Financiado
PANORAMA DE LA MUTAGENESIS GENOMICA RESULTANTE DE LOS DEFECTOS EN LA REPARACION...
PANORAMA DE LA MUTAGENESIS GENOMICA RESULTANTE DE LOS DEFECTOS EN LA REPARACION DEL ADN EN TUMORES HUMANOS CANCER SEQUENCING EFFORTS HAVE YIELDED A REPOSITORY OF HUMAN GENOMIC DATA OF AN UNPRECEDENTED SCALE, WHICH KEEPS GROWING BY THE DAY, THE MAIN MOTIVATION BEHIND SEQUENCING THE CANCER GENOMES WAS TO DISCOVER NEW CANCER DRIVER MUTAT... CANCER SEQUENCING EFFORTS HAVE YIELDED A REPOSITORY OF HUMAN GENOMIC DATA OF AN UNPRECEDENTED SCALE, WHICH KEEPS GROWING BY THE DAY, THE MAIN MOTIVATION BEHIND SEQUENCING THE CANCER GENOMES WAS TO DISCOVER NEW CANCER DRIVER MUTATIONS, HOWEVER THE SAME TUMOR GENOMIC DATA LENDS ITSELF TO A VARIETY OF OTHER TYPES OF STATISTICAL ANALYSES, FOR INSTANCE, MUTATIONAL PROCESSES CAN BE ANALYZED BY LOOKING AT PASSENGER (NON-SELECTED) MUTATIONS IN CANCER GENOMES TO ELUCIDATE MECHANISMS OF MUTAGENESIS AND DNA REPAIR IN HUMAN SOMATIC CELLS, IN LINE WITH THIS THEME, THIS PROJECT CONSISTS OF A SYSTEMATIC, RIGOROUS STATISTICAL ANALYSES OF MASSIVE CANCER GENOMIC DATA SETS (ALSO, GENOMES OF HEALTHY SOMATIC CELLS AND OF CANCER CELL LINES) TO GAIN A BETTER UNDERSTANDING OF MUTAGENIC PROCESSES, IN PARTICULAR, WE PROPOSE TO EXAMINE THEIR GENOME-WIDE MUTATIONAL FOOTPRINTS, DEFINED IN MULTIPLE WAYS, IN CANCER GENOMIC DATA TO LEARN ABOUT MECHANISMS OF DNA REPAIR AND ITS FAILURES, WE WILL PLACE AN EMPHASIS ON DNA MISMATCH REPAIR (MMR) PATHWAY AND THE HOMOLOGOUS RECOMBINATION REPAIR (HRR) PATHWAYS, WHICH COMMONLY FAIL IN TUMOR AND WHICH SIGNIFICANTLY INCREASE MUTATION RATES THUS DRIVING CANCER EVOLUTION, WE WILL DEVELOP AND TEST NOVEL STATISTICAL METHODOLOGIES TO DETECT AND CLASSIFY GENOMIC MUTATION PATTERNS THAT RESULT FROM FAILED DNA REPAIR AND THAT ARE ORTHOGONAL BEYOND THE STANDARD TRINUCLEOTIDE MUTATIONAL SPECTRA, RESULTING MUTATION PATTERNS WILL ALLOW US TO TEST OUR PRINCIPAL HYPOTHESES THAT THERE ARE MULTIPLE WAYS IN WHICH MMR AND HRR PATHWAYS BECOME DEFICIENT, THAT THEY BREAK DOWN IN MORE CANCER CASES THAN IS CURRENTLY RECOGNIZED, AND THAT SUCH DIVERSE AND WIDESPREAD DEFICIENCY IMPACTS CANCER EVOLUTION AND RESPONSE TO CANCER TREATMENT, OUR PROJECT MAY HAVE VARIOUS IMPLICATIONS TO CANCER PREVENTION AND THERAPY, AS WELL AS FOR UNDERSTANDING MUTAGENIC MECHANISMS IN HUMAN CELLS, GENOMICA\CANCER\REPARACION DEL ADN\FIRMAS MUTACIONALES ver más
01/01/2020
FUNDACIO INSTITUT...
182K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2020-01-01
Presupuesto El presupuesto total del proyecto asciende a 182K€
Líder del proyecto
FUNDACIO INSTITUT DE RECERCA BIOMEDICA IRB BA... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5 23M