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dc.contributor.authorBuj, Raquel
dc.contributor.authorMallona, Izaskun
dc.contributor.authorDíez Villanueva, Anna
dc.contributor.authorBarrera, Víctor
dc.contributor.authorMauricio Puente, Dídac
dc.contributor.authorPuig-Domingo, Manuel
dc.contributor.authorReverter, Jordi L.
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorAzuara, Daniel
dc.contributor.authorRamírez, Jose L.
dc.contributor.authorAlonso, Sergio
dc.contributor.authorRosell, Rafael
dc.contributor.authorCapellà, Gabriel
dc.contributor.authorPerucho, Manuel
dc.contributor.authorRobledo, Mercedes
dc.contributor.authorPeinado, Miguel A.
dc.contributor.authorJordà, Mireia
dc.description.abstractHypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation. QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types. Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits. In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings.ca_ES
dc.description.sponsorshipRB was supported by a FPI fellowship from Ministerio de Economía y Competitividad. AD-V was supported in part by a contract PTC2011-1091 from Ministerio de Economía y Competitividad. This work was supported by grants from FEDER, the Ministerio de Economía y Competitividad (SAF2011/23638 to MAP), the Instituto de Salud Carlos III (FIS PI11/02421 to JR, FIS PI11/01359 and FIS PI14/00240 to MR, FIS PI14/00308 to MJ, FIS PI12/00511 to MP), and Fundació Olga Torres (to MJ).ca_ES
dc.publisherImpact Journalsca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofOncotarget, 2016, vol. 7, núm. 9, p. 10536-10546ca_ES
dc.rightscc-by (c) Buj et al., 2016ca_ES
dc.subjectDNA hypomethylationca_ES
dc.subjectAlu repeatsca_ES
dc.subjectHuman cancerca_ES
dc.titleQuantification of Unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samplesca_ES

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