A new whole genome amplification method for studying clonal evolution patterns in malignant colorectal polyps.

Genes, Chromosomes & Cancer
Daniela HirschTimo Gaiser

Abstract

To identify the genetic drivers of colorectal tumorigenesis, we applied array comparative genomic hybridization (aCGH) to 13 formalin-fixed paraffin-embedded (FFPE) samples of early, localized human colon adenocarcinomas arising in high-grade adenomas (so-called "malignant polyps"). These lesions are small and hence the amount of DNA is limited. Additionally, the quality of DNA is compromised due to the fragmentation as a consequence of formalin fixation. To overcome these problems, we optimized a newly developed isothermal whole genome amplification system (NuGEN Ovation® WGA FFPE System). Starting with 100 ng of FFPE DNA, the amplification system produced 4.01 ± 0.29 μg (mean ± standard deviation) of DNA. The excellent quality of amplified DNA was further indicated by a high signal-to-noise ratio and a low derivative log(2) ratio spread. Both, the amount of amplified DNA and aCGH performance were independent of the age of the FFPE blocks and the associated degradation of the extracted DNA. We observed losses of chromosome arms 5q and 18q in the adenoma components of the malignant polyp samples, while the embedded early carcinomas revealed losses of 8p, 17p, and 18, and gains of 7, 13, and 20. Aberrations detected in the adeno...Continue Reading

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Citations

Mar 20, 2012·Biochimica Et Biophysica Acta·Thomas RiedJordi Camps
Aug 4, 2015·Pharmacogenomics·Elena Puerta-GarcíaMiguel Ángel Calleja-Hernández
Dec 10, 2013·Genomics·L HawthornW Mojica
Jun 28, 2017·Journal of Clinical Gastroenterology·Christian GalataKaroline Horisberger
Jul 4, 2018·The Journal of Pathology·Malgorzata A KomorUNKNOWN NGS-ProToCol Consortium:
Sep 20, 2018·International Journal of Cancer. Journal International Du Cancer·David FiedlerTimo Gaiser
Sep 27, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hai-Ming HuWenhua Li
Aug 15, 2019·International Journal of Cancer. Journal International Du Cancer·Malgorzata A KomorUNKNOWN NGS-ProToCol Consortium
May 26, 2016·Cancer Prevention Research·Ester BorrasEduardo Vilar
Jul 4, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniela HirschTimo Gaiser
Dec 16, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Daniela HirschTimo Gaiser
Apr 1, 2017·Current Opinion in Systems Biology·Christopher AbboshCharles Swanton

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