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How a New Method is Improving Whole Genome Sequencing of FFPE Tumor Tissues

In this webinar, experts from WuXi NextCODE discuss extraction methodology that allows scientists and researchers to gather maximum value for FFPE sequencing.

Formalin-fixed paraffin-embedded (FFPE) tissue samples are an important source of information for cancer researchers and are more readily available than frozen tumor samples collected from patients. These tissues allow for advancements in cancer treatment and prevention because they are backed with a wealth of clinical and outcome data enabling novel insights.

Now, researchers are able to more effectively analyze these FFPE tissue samples through the application of whole-genome sequencing (WGS) using next-generation sequencing (NGS) technology. NGS technology, however, has been restricted to frozen tumors. Using WGS for FFPE tissue samples is also made more difficult because of a number of factors from fragmented DNA and sequencing libraries with low complexity, to uneven genomic coverage and sequencing artifacts that are a result of the fixation method used.

To overcome these challenges, NGS of these samples require a high level of attempted sequencing coverage in order to compensate for the uneven coverage. WuXi NextCODE scientists Dr. Richard Williams and Dr. Shannon T. Bailey believe they have found the fix to this problem.

WuXi NextCODE SeqPlus

WuXi NextCODE’s SeqPlus is a nucleic acid extraction methodology that allows scientists and researchers to gather maximum value for FFPE sequencing compared to previous techniques. To understand more about SeqPlus, watch this free on-demand webinar from WuXi NextCODE , a genomic information company that uses sequencing data to improve people’s health around the globe.

FFPE tissues are most commonly sourced from archival material. During a patient’s course of treatment, FFPE samples are taken, stored, used and studied. It is inexpensive to create large samples and easy to maintain and preserve this library because they can be stored in a cabinet at room temperature.

However, proteins present in FFPE tissue samples are denatured during the fixing process, which can limit their application in

certain types of immunohistochemistry studies. Furthermore, the nucleic acids in the FFPE tissue samples are not well preserved either and are often heavily fragmentated and limited in quantity.

WuXi NextCODE’s SeqPlus is capable of using original samples to unlock insights into previously-collected samples that have been of limited use due to restrictions of technology. They now have the technology to obtain high quality WGS read outs from FFPE samples.

DNA extracted by the SeqPlus method results in at least 20 times the coverage for 98 percent of the genome. The advantages of this method include the ability to unlock new insights, supporting research into more targeted therapies, all while taking less time.

This method was validated using 15-year-old archival tissue samples that were provided by the National Cancer Institute (NCI). WuXi NextCODE’s SeqPlus was able to consistently confirm the presence of mutations in the DNA sequences from these samples which had been previously identified using traditional methods.

Xtalks spoke with Dr. Shannon T. Bailey, the Associate Director of Cancer Genetics at WuXi NextCODE, to understand the significance of these findings. “An important point that I want to make is that these are older samples. Most of what you’ll see with FFPE is that people typically look at younger samples — like a year or two [in age]. Going back 15 years is actually quite an accomplishment,” he said.

When discussing the importance of fixed tissues with Bailey, he said that the collection and fixation method of these tissues is particularly advantageous because scientists and researchers can use them almost indefinitely. In previous attempts to use WGS to analyze conventionally fixed tissues, the sequence needed to be looked at very deeply in order to make it work. But now more than ever, SeqPlus is becoming important in studying archival tissues.

“SeqPlus is a proprietary method for isolation of DNA as well as improvements in the library prep step of the sequencing workflow,” said Bailey. “So, what this method does is allow you to obtain high molecular weight DNA fragments.”

“Historically when you isolate DNA from FFPE tissues, the DNA is mostly fragmented into very small pieces, which we’ve learned doesn’t allow itself to be sequenced that well. But with SeqPlus, you extract much higher molecular weight fragments, and that is really the reason why we’re able to provide good sequencing coverage – the DNA is mostly intact,” said Bailey.

Written by: Mira Nabulsi

Published on: December 2, 2019

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