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Intra-tumour heterogeneity : going beyond genetics

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dc.contributor.authorCaiado, Francisco
dc.contributor.authorSilva-Santos, Bruno
dc.contributor.authorNorell, Haakan
dc.date.accessioned2021-05-26T10:20:56Z
dc.date.available2021-05-26T10:20:56Z
dc.date.issued2016
dc.description© 2016 Federation of European Biochemical Societiespt_PT
dc.description.abstractCancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub-clones in the mutating tumour. Novel cancer cell variants build upon the pre-existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non-genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra-tumour heterogeneity, before dissecting four major interdependent non-genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non-genetic factors to intra-tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single-cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra-tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non-genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival.pt_PT
dc.description.sponsorshipOur work was funded by Associação Portuguesa Contra a Leucemia (APCL-SEMAPA 2014 to HN) and Fundação para a Ciência e Tecnologia (FCT) through individual fellowships (SFRH/BPD/91344/2012 to FC; SFRH/BCC/105888/2014 and SFRH/BPD/112968/2015 to HN) and a FCT research grant (EXPL/BIM-ONC/1656/2013 to HN).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFEBS J. 2016 Jun;283(12):2245-2258pt_PT
dc.identifier.doi10.1111/febs.13705pt_PT
dc.identifier.eissn1742-4658
dc.identifier.issn1742-464X
dc.identifier.urihttp://hdl.handle.net/10451/48177
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationDEVELOPMENT OF CLONAL CANCER CELL ESCAPE VARIANTS AS THE BASIS FOR RELAPSE IN ACUTE MYELOID LEUKEMIA
dc.relationQuantitative dissection of tumor recurrence by cellular barcoding: Preprogrammed versus stochastic subclonal dynamics and genome evolution
dc.relationQuantitative analysis of clonal evolution and characterization of tumor escape variants in relapsing Acute Myeloid Leukemia
dc.relation.publisherversionhttps://febs.onlinelibrary.wiley.com/journal/17424658pt_PT
dc.subjectCancer mutationpt_PT
dc.subjectCancer stem cellspt_PT
dc.subjectClonal evolutionpt_PT
dc.subjectLeukaemia initiating cellspt_PT
dc.subjectLineage tracingpt_PT
dc.subjectNext-generation sequencingpt_PT
dc.subjectNon-genetic variabilitypt_PT
dc.subjectPopulation dynamicspt_PT
dc.subjectSingle-cell transcriptomicspt_PT
dc.subjectSub-clonept_PT
dc.titleIntra-tumour heterogeneity : going beyond geneticspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BPD/91344/2012
oaire.awardNumberSFRH/BCC/105888/2014
oaire.awardNumberSFRH/BPD/112968/2015
oaire.awardNumberEXPL/BIM-ONC/1656/2013
oaire.awardTitleDEVELOPMENT OF CLONAL CANCER CELL ESCAPE VARIANTS AS THE BASIS FOR RELAPSE IN ACUTE MYELOID LEUKEMIA
oaire.awardTitleQuantitative dissection of tumor recurrence by cellular barcoding: Preprogrammed versus stochastic subclonal dynamics and genome evolution
oaire.awardTitleQuantitative analysis of clonal evolution and characterization of tumor escape variants in relapsing Acute Myeloid Leukemia
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F91344%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBCC%2F105888%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F112968%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBIM-ONC%2F1656%2F2013/PT
oaire.citation.endPage2258pt_PT
oaire.citation.issue12pt_PT
oaire.citation.startPage2245pt_PT
oaire.citation.titleThe FEBS Journalpt_PT
oaire.citation.volume283pt_PT
oaire.fundingStreamSFRH
oaire.fundingStream3599-PPCDT
person.familyNameCaiado
person.familyNameSilva-Santos
person.familyNameNorell
person.givenNameFrancisco
person.givenNameBruno
person.givenNameHaakan
person.identifier.ciencia-idD51E-6517-BE6A
person.identifier.orcid0000-0003-4096-4448
person.identifier.orcid0000-0003-4141-9302
person.identifier.orcid0000-0001-5232-7660
person.identifier.scopus-author-id23033354600
person.identifier.scopus-author-id6505885924
person.identifier.scopus-author-id12759727600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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