2024-03-28T13:03:15Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/107972021-05-20T06:34:16Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Buj, Raquel
author
Mallona, Izaskun
author
Díez-Villanueva, Anna
author
Barrera, Víctor
author
Mauricio, Dídac
author
Puig-Domingo, Manel
author
Reverter, Jordi L
author
Matias-Guiu, Xavier
author
Azuara, Daniel
author
Alonso, Sergio
author
Rosell, Rafael
author
Capellà, Gabriel
author
Perucho, Manuel
author
Robledo Batanero, Mercedes
author
Peinado, Miguel A
author
Jordà, Mireia
author
Reverter, Jordi L.
author
Ramírez, Jose L
author
Peinado, Miguel A.
author
2016-03-01
Hypomethylation 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.
Oncotarget .2016 ;7(9):10536-46.
http://hdl.handle.net/20.500.12105/10797
26859682
10.18632/oncotarget.7233
1949-2553
Oncotarget
Quantification of unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples.