CancerDetect®

Highly Sensitive Detection of Actionable Variants from Liquid Biopsy with Low Tumor Content

Liquid biopsy analysis represents an optimal alternative testing procedure in cases where no tumor tissue is available, for example, with irresectable tumor or poor patient conditions. The main target of Liquid biopsy analysis is cell-free DNA (cfDNA) which is released into the bloodstream by necrotic and apoptotic cells. Elevated levels of cfDNA have been reported in patients with cancer and other types of diseases. The circulating cfDNA is released from both normal and tumor cells. The fraction of tumor-derived cfDNA (circulating tumor DNA/ctDNA) differs from patient to patient, depending on tumor entity, tumor stage, tumor burden, and other factors. Since only a fraction of circulating DNA is derived from the tumor, highly sensitive methods are required to detect minimal ctDNA concentrations. We at CeGaT established our CancerDetect® panel using UMI-based technology, which detects sequence variants in actionable, most prevalent hotspots. Moreover, due to non-invasive and repeatable sampling, CancerDetect® represents a great approach to monitoring. By very sensitive detection of tumor-specific biomarkers, the analysis of ctDNA can be used as a surrogate marker for treatment response during medical follow-up.

CeGaT’s CancerDetect® panel is ideally suited for monitoring and follow-up of tumor disease.

Fast

Processing time: 2-3 weeks after sample receipt

Trusted

Highest confidentiality and quality standards

Dedicated

Our customer service accompanies you at each single step

Service Details

We will report all relevant findings in a medical report. This includes a list of all identified clinically relevant variants. These variants are clearly annotated with gene name, functional category of the mutation, transcript-ID, allele frequency, and effect on protein function. Each single medical report is prepared and discussed by an interdisciplinary team of scientists and physicians to guarantee highest quality.

Liquid biopsy enables the detection of variants with potential therapeutic relevance in patients where tumor is inaccessible, allowing tumor characterization and disease monitoring
Highly sensitive and accurate detection of actionable, most prevalent driver mutations in 36 genes with very low allele frequencies by using UMI-based technology (NAF ≥0.25%)
High coverage: 50,000 – 100,000x raw coverage
Simple, non-invasive and repeatable sampling provides best conditions for longitudinal follow-up testing
By very sensitive detection of tumor-specific biomarkers, the analysis of ctDNA can be used to monitor treatment response and drug resistance
Processing time: 2- 3 weeks from sample receipt

Our Standard Sample Requirements

3x 10 ml cfDNA tubes for liquid biopsy

The volume needed for liquid biopsy can depend on the sample type. 3x 10 ml are recommended for blood-based liquid biopsy. While it can be more for e.g. Aszite or less e.g. for liquor. We are happy to assist you for the individual case. Please contact us at tumor@cegat.de.

CancerDetect® can generally also be used for non- liquid biopsy based approaches. In case you are interested please contact us with your case specifics.

Sample Report

Download sample report (PDF)

Process for Diagnostics

Test selection

We are happy to assist in choosing the suitable diagnostic strategy

Sampling & consultation

The patient receives genetic counseling and signs the order and consent form. Patient samples are retrieved and, together with the order form, send to CeGaT.

Analysis

CeGaT performs the requested analysis and issues the medical report.

Genetic consultation

Results are discussed with the patient.

The Power of Liquid Biopsy Testing

Liquid Biopsy analysis represents an optimal alternative testing procedure in cases where tumor tissue is unavai-lable, e.g., irresectable tumors or poor patient conditions. The main target of Liquid Biopsy analysis is cell-free DNA (cfDNA) which is increasingly released into the bloodstream by necrotic and apoptotic cells in patients with cancer and other types of diseases. Circulating cfDNA is released from both normal and tumor cells. The fraction of tumor-derived cfDNA (circulating tumor DNA/ctDNA) depends on tumor entity, tumor stage, tumor burden, and other factors and therefore is not the same in every patient. Since only a fraction of circulating cfDNA is derived from the tumor, highly sensitive methods are required to detect minimal ctDNA concentrations.

CeGaT has established and validated extensive Liquid Biopsy panels assessing cell-free DNA. CancerPrecision® uses Liquid Biopsy testing to provide a complete genetic profile of the patient’s tumor, supporting the choice of the best possible therapy. A tumor content of at least 20% is required for this analysis. Since the content of ctDNA can be less than 20%, CeGaT also offers CancerDetect®, a duplex UMI-based panel. CancerDetect® identifies sequence vari-ants in actionable, most prevalent driver mutations with an allele frequency above 0.25%. This highly sensitive detec-tion of tumor-specific biomarkers represents an excel-lent tool for monitoring treatment response and minimal residual disease. In addition, the method’s high sensitivity makes failure much less likely, even with a low tumor fraction in the sample.

Your Benefits

Variants with Potential Therapeutic Relevance
An increasing number of tumor therapies are available or currently tested in clinical trials. Many of these treatments address signaling pathways. Thus, identifying genetic mutations or affected cellular pathways is an essential factor for personalizing the patient’s treatment and finding new treatment options.
Detection of Drug Resistance
Especially the development of drug resistance, which may occur after initial treatment, represents a considerable obstacle in cancer management. Exposed to treatment, some tumor cells might acquire additional mutations proving growth advantage to subclonal tumor cell population. Our CancerDetect® panel offers the possibility to track known resistance-associated mutations and adjust the treatment regime before the outgrowth of a resistant tumor. For optimal results we recommend to test prior and during the treatment on a regular basis.

Detection of Recurrence
Using UMI-based high sensitivity molecular genetic analysis, CancerDetect® may detect tumor recurrence earlier than conventional methods. CancerDetect® may thus help physicians to monitor minimal residual disease and to detect relapse at an early stage. Therefore testing on a regular basis is recommended.
Unique Molecular Identifier Technology
The implemented UMI-based technology allows for the detection of mutations in targeted regions already at a very low fraction. The introduction of unique molecular identifiers prior to PCR increases the sensitivity and accuracy of sequencing and reduces false-positive results. Using this technology, we are able to highly increase sensitivity and detect variants as low as 0.25% novel allele frequency.

Gene Directory

All relevant variants in a named exon are analyzed. Exon numbers refer to coding exons (CDS) of the respective gene. The diagnostic is not limited to the listed example hotspot mutations. Exons not named and all variants within are not part of the analysis.

Gene	NM_Nr.	Enriched region (incl. example hotspot (HS)-variants)
AKT1	NM_005163	Exon 2 (HS E17)
ALK	NM_004304	Exons 21-25 (incl. HS F1174)
ARAF	NM_001654	Exon 6 (HS S214)
BRAF	NM_004333	Exons 11 and 15 (incl. HS V600)
CTNNB1	NM_001904	Exon 2 (incl. HS S37, S45)
EGFR	NM_005228	Exons 18-21 (incl. HS E746_A750del, T790, L858)
ERBB2	NM_004448	Exon 8, 19-21 (incl. HS V842)
ERBB3	NM_001982	Exons 3, 6-9, 23 (incl. HS V104, E928)
ERBB4	NM_005235	Exon 12 (incl. HS E452)
ESR1	NM_000125	Exons 4-8 (incl. HS K303, Y537, D538)
FGFR2	NM_000141	Exons 6, 8, 11 (incl. HS S252, N549)
FGFR3	NM_000142	Exon 12 (HS V555)
GNA11	NM_002067	Exon 5 (HS Q209)
GNAQ	NM_002072	Exon 5 (HS Q209)
GNAS	NM_000516	Exon 8 (HS 201) and Exon 9 (HS Q227)
H3-3A	NM_002107	Exon 1 (HS K27 and G34)
H3-3B	NM_005324	Exon 1 (HS K37)
HRAS	NM_005343	Exons 1-3 (incl. HS G12, Q61)
IDH1	NM_005896	Exon 2 (HS R132)

Gene	NM_Nr.	Enriched region (incl. example hotspot (HS)-variants)
IDH2	NM_002168	Exon 4 (HS R140, R172)
JAK2	NM_004972	Exon 12 (HS V617)
KIT	NM_000222	Exons 9, 11, 13, 14, 17, 18 (incl. HS W557_K558del, D816)
KRAS	NM_004985	Exons 1-3 (inkl. HS G12, Q61)
MAP2K1	NM_002755	Exon 3 (HS P124)
MET	NM_001127500	Exon 18 (incl. HS Y1248, Y1253)
MYCN	NM_005378	Exon 1 (HS P44)
NRAS	NM_002524	Exons 1-3 (inkl. HS G12, Q61)
PDGFRA	NM_006206	Exons 4, 9, 11, 13, 17 (incl. HS D842)
PIK3CA	NM_006218	Exons 4, 7, 9, 13, 20 (incl. HS E542, E545, H1047)
PTEN	NM_000314	Exons 5-7 (incl. R130, R233)
RAC1	NM_018890	Exon 2 (HS P29)
RAF1	NM_002880	Exon 6 (incl. HS S257, S259)
RET	NM_020975	Exon 10, 11, 13-16 (incl. HS C634)
STAT5B	NM_012448	Exon 15 (HS N642)
TERT	NM_198253	Promotor HS c.-124 (C228), c.-146 (C250)
TP53	NM_000546	Entire coding region

Knowledge

Webinar

Genetic tumor diagnostics – the information basis for treatment decisions

In this webinar recording, our specialists will explain the possibilities and limitations of molecular genetic tumor diagnostics. Saskia Biskup (MD., Ph.D.) and Stefan Griesbach (Ph.D.) will present current approaches in the field of precision oncology and show how genetic diagnostics can support you in determining the best therapy for your patients.

CancerDetect®

Liquid biopsy in genetic tumor diagnostics –
CancerDetect®

In precision oncology, the genotyping of the tumor represents a very essential diagnostic step to guide treatment decisions. But it can be difficult or impossible to obtain a tumor sample, for example, in case of unresectable tumors or poor patient condition. Our colleague Dr. Olga Rataj explains how we address this issue with CancerDetect®.