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Updated: May 24, 2026

Comparative Lesions Analysis Through a Targeted Sequencing Approach
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Published on: November 5, 2019

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

Daniela Hirsch1, Jordi Camps, Sudhir Varma

  • 1Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Genes, Chromosomes & Cancer
|February 16, 2012
PubMed
Summary

This study optimized whole genome amplification for formalin-fixed paraffin-embedded DNA, enabling array comparative genomic hybridization (aCGH) to identify genetic drivers in colorectal cancer progression. Findings revealed specific chromosomal aberrations linked to adenoma-carcinoma transition.

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Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

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Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Pathology

Background:

  • Colorectal tumorigenesis involves complex genetic alterations.
  • Analyzing early-stage colorectal cancer (CRC) using formalin-fixed paraffin-embedded (FFPE) samples is challenging due to limited and degraded DNA.
  • Array comparative genomic hybridization (aCGH) is a powerful tool for detecting genomic imbalances.

Purpose of the Study:

  • To optimize whole genome amplification (WGA) for FFPE DNA to enable high-quality aCGH analysis.
  • To identify genetic drivers and chromosomal aberrations in early colorectal adenocarcinomas within malignant polyps.
  • To investigate the clonal relationship between adenoma and carcinoma components in malignant polyps.

Main Methods:

  • Optimized an isothermal WGA system (NuGEN Ovation® WGA FFPE System) for FFPE DNA.
  • Applied aCGH to 13 FFPE samples of early colon adenocarcinomas arising in high-grade adenomas.
  • Assessed DNA quality, quantity, and aCGH performance post-amplification, independent of FFPE block age.

Main Results:

  • The WGA system successfully amplified degraded FFPE DNA (100 ng to >4 µg) with excellent quality.
  • aCGH performance was robust, unaffected by DNA fragmentation or FFPE block age.
  • Identified distinct chromosomal aberrations: losses of 5q and 18q in adenomas, and losses of 8p, 17p, 18, and gains of 7, 13, 20 in carcinomas.
  • Aberrations in adenomas were retained in carcinomas, suggesting clonal evolution.
  • Gain of chromosome arm 20q was associated with progression from adenoma to carcinoma.

Conclusions:

  • Isothermal WGA of FFPE DNA is technically suitable for aCGH in cancer research.
  • This method facilitates the identification of genetic alterations driving colorectal tumorigenesis.
  • Specific chromosomal gains, such as 20q, serve as indicators of malignant progression in colorectal polyps.