Molecular Heterogeneity

Cancer is now known to be extremely complex at the molecular level. Both inter-tumoral and intra-tumoral genomic variation exists where multiple driver elements are present and can change during the tumor's evolution. Single gene analysis can be time consuming and inefficient because it provides insufficient information to appreciate a tumor’s heterogeneity.

“Sequencing cancer samples with Ion AmpliSeq™ gene panels and the Ion PGM™ sequencer, you can describe heterogeneity of samples according to the mutations found in the sub-populations. This is impossible to do with current methods.”

Aldo Scarpa, MD, PhD 
Professor of Pathology Director 
Department of Pathology and Diagnostics Director 
ARC-NET Research Centre for Applied Research on Cancer University of Verona 
Life Technologies OncoNetwork Consortia Member

“That’s why we need to have a panel that allows us to identify all the mutations, all of the molecular alterations, that are present in the specific tumor, so we can really see the molecular landscape of each individual tumor.”

Nicola Normanno, MD, PhD
Director, Research Department Centro di Ricerche Oncologiche di Mercogliano
Mercogliano (AV) and INT-Fondazione Pascale
Naples, Italy
Life Technologies OncoNetwork Consortia Member
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Long turnaround times for results

When developing assays that may be used for future clinical use, it is important to consider the time-to-results. Although next-generation sequencing can produce highly informative data for clinical research, some next-generation systems require several days to generate results. This can make applying next-generation sequencing assays prohibitive in possible future clinical applications.

"Ion PGM System with AmpliSeq™ technology has allowed us to substantially improve the turnaround time and cost of sequencing these important genes—BRCA1 and BRCA2."

José Luis Costa, PhD
Postdoctoral Fellow, Institute of Molecular Pathology and Immunology
Porto, Portugal
Life Technologies BRCA1 and BRCA2 Consortia Member
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Cumbersome workflows and lack of complete solution

Laboratory space and funding for cancer research can be limited. Cancer research labs can benefit from robust, complete systems that can perform multiple genetic analysis applications.

“Sequencing gene panels with Ion Torrent™ is complete. You have the Ion AmpliSeq™ gene selection technology, the Ion PGM™ sequencing machine and also the Ion Reporter™ analysis software. For me, it is important to have a whole integrated solution so researchers can advance from the tumor to results.”

Pierre Laurent-Puig, MD, PhD
Professor, Paris-Descartes University Medical School
Paris France
Life Technologies OncoNetwork Consortia Member
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Ability to sequence challenging samples

An important area of consideration for genomic analysis technologies used in clinical research is the robustness and accuracy of the system. Clinical and translational research will require genomic analysis systems to be reliable if they are to be considered for future clinical applications.

“The methodology proved robust enough to call even difficult mutations, including homopolymers of 6-8 bases in BRCA1 and BRCA2 genes.”

José Luis Costa, PhD
Postdoctoral Fellow, Institute of Molecular Pathology and Immunology
Department of Pathology and Diagnostics Director 
Porto, Portugal
Life Technologies OncoNetwork Consortia Member
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Difficulty extracting DNA from small FFPE samples

Preserving tumor tissue using the formalin fixed paraffin embedded (FFPE) process is common practice. However, the FFPE process can introduce challenges affecting the extraction, quality, and yield of tumor DNA available for subsequent genomic analysis applications. Because of these challenges, cancer researchers need reliable sequencing systems that consume as little tumor DNA as possible.

“Using other technologies, for every PCR reaction we would need 10 ng of DNA, and now with Ion AmpliSeq™ Colon and Lung Cancer panel, we can interrogate tens of genes in one reaction—just 10 ng.”

Marjolijn Ligtenberg, PhD
Associate Professor, Head of Laboratory Tumor Genetics,
Radboud University Nijmegen Medical Centre
Nijmegen, the Netherlands
Life Technologies OncoNetwork Consortia Member

“You can get results on 20, 30, 40 genes by using 10 ng of DNA from formalin fixed paraffin embedded tissue.”

Nicola Normanno, MD, PhD
Director, Research Department
Centro di Ricerche Oncologiche di Mercogliano
Mercogliano (AV) and INT-Fondazione Pascale
Naples, Italy
Life Technologies OncoNetwork Consortia Member

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Identifying actionable genomic information

The application of whole genome sequencing in basic research is generating a deluge of new information about cancer genomic variants, much of which is of unknown clinical significance. Sorting the drivers from passenger mutations is an important challenge for cancer researchers. In addition, it is important to conduct research on variants that may be clinically actionable in the future.

“The addition of Oncomine™ annotations to Ion Reporter™ Software provides the best way to prioritize those mutations that are likely cancer drivers, based on well-curated, supporting evidence across cancer types.”

Scott Tomlins, MD, PhD
Assistant Professor, Department of Pathology University of Michigan

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