Comprehensive NGS panel for inherited cancer research
GALEAS™ HereditaryPlus (RUO)
A NGS panel with optimised bioinformatics for research analysis of germline variants associated with hereditary cancers - including Lynch syndrome.
GALEAS HereditaryPlus is for research use only and not for use in diagnostic procedures outside of the UK. For diagnostic applications, please see our GALEAS HereditaryPlus (UKCA) product.
Complete hereditary cancer analysis at your fingertips.
Between 5-10% of all cancers, including those of the breast, ovary, uterus, prostate, and gastrointestinal system can be accounted for by hereditary cancers.1
Genetic research therefore plays a crucial role in understanding the variants within cancer susceptibility genes and their association with hereditary cancer risk.
Whilst multi-gene next generation sequencing (NGS) panels have emerged as a widely adopted research approach for the investigation of heritable cancers. Many targeted NGS panels struggle to identify important Copy Number Variations (CNVs). They often require additional techniques, for example multiplex ligation dependent probe amplification (MLPA) analysis to detect them.
GALEAS HereditaryPlus combines an innovative NGS panel design with optimised secondary bioinformatics to overcome this limitation. It offers a single assay that supports the analysis of not only single nucleotide variants (SNVs) and insertions and deletions (INDELs) but a wide range of important copy number variants (CNVs). As such it offers research laboratories the potential to streamline workflows by reducing the need for additional orthogonal assays such as MLPA.
Key features
- 146 genes with known associations to hereditary cancers including paediatric cancers
- Content informed by genes listed in the UK National genomic test directory
- 100% recall for SNVs and INDELs recall and annotation, including in challenging PMS2 regions
- Enhanced CNV calling from single exon to whole gene alterations
- Allows for own panel of normals for noise correction and optimum sensitivity in CNV calling
- Identity tracking with 24 carefully selected SNPs
- Cloud-based variant calling pipelines to ensure accurate calling and downstream research analysis
- Compatible with downstream data analysis and interpretation software
Comprehensive coverage of key genes
GALEAS HereditaryPlus is a comprehensive NGS panel that delivers coverage of 146 genes well-established in their associations with hereditary cancer. From key cancer syndromes like Lynch Syndrome to rarer hereditary cancer types like Phaeochromocytoma and paediatric cancers like Wilms tumor, GALEAS HereditaryPlus ensures a comprehensive understanding of the genetic landscape.
Table 1: Genes included in GALEAS HereditaryPlus design.
| Breast | ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, TP53 |
| Colon | APC, AXIN2, BMPR1A, CHEK2, EPCAM, GREM1, MLH1, MSH2, MSH6, PMS2, MSH3, MUTYH, NTLH1, POLD1, POLE, PTEN, RNF43, SMAD4, STK11, TP53 |
| Renal | BAP1, FH, FLCN, MET, SDHB, VHL |
| Ovarian | ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, SKT11, TP53, RAD51C, RAD51D |
| Prostate | ATM, BRCA1, BRCA2, CHEK2, MLH1, MSH2, MSH6, PALB2 |
| Gastric/GIST | CDH1, KIT, PDGFRA, SDHC, SDHD, SDHA |
| Brain | APC, ATM, MLH1, MSH2, MSH6, PMS2, TP53 |
| Sarcoma | EXT1, EXT2, MTAP, NF1, RECQL4, SQSTM1, TP53 |
| Pediatric (Wilms tumor) | CDKN1C, CTR9, REST, TRIM28, WT1 |
GALEAS HereditaryPlus offers high analytical performance for variant detection
The combination of careful design and state of the art bioinformatics pipelines supports the accurate detection of SNVs, INDELs and a wide range of CNVs without the need for orthogonal assays such as Sanger sequencing or MLPA analysis in research workflows. This NGS panel demonstrates high analytical performance for hereditary cancer research applications regardless of variant or cancer type.
- SNVs: Delivers reliable identification of SNVs including direct genotyping of the MSH2 c.942+3A>T variant avoiding the need for Sanger sequencing and streamlining workflows
- INDELs: Accurately detects both small and large indels, including those exceeding 10 base pairs
- CNVs: Reliably and robustly identifies CNVs from single exons to whole genes and mosaic copy number variation potentially eliminating the need for MLPA in hereditary cancer research
Overcoming challenges: CNVs and mosaics
While many NGS panels are designed to detect SNVs and small INDELs, the characterisation of CNVs from sequencing data can be technically challenging and is often supported by complementary research methods.
GALEAS HereditaryPlus combines an expertly constructed probe design together with optimised bioinformatics pipelines to support laboratories in the research-based analysis of:
- A range of CNV events, from single exon to whole gene changes
- Mosaic copy number variantion in key genes, including APC and TSC2
- Detect the PMS2 gene
In a study using 64 samples with orthogonal data, GALEAS HereditaryPlus delivered an analytical sensitivity of 98.3% and an analytical specificity of 99% for CNV analysis. This high level of sensitivity and specificity guarantees the identification of critical genetic alterations associated with hereditary cancer, supporting researchers with high-quality genomic data for further investigation.
Boland inversions, BRCA2 and STK11 large deletions and AluY repeats
GALEAS Hereditary Plus was able to detect a Boland Inversion, BRCA2 and STK11 large deletetions when a combination of short range and long range paired-end mapping and split read analysis was used with SeraCare Inherited Cancer DNA mix v2. An Alu specific module using repeat masking allowed successful calling of the BRCA2 AluY insertion.
Why choose GALEAS HereditaryPlus?
Reduce reliance on ancillary assays such as MLPA or Sanger sequencing
Enable detection of a broad range of variant types, including MSH2 c.942+3A>T variant and a wide range of CNVs in genes such as APC, MHS2, BRCA1 and PMS2, using a single NGS-based workflow.
Study genetic variation in rare as well as common hereditary cancer
Coverage of genes associated with a broad range of hereditary cancers from breast, and prostate, Lynch Syndrome and Wilms tumor, help to reduce operational complexity, time and cost.
Streamline bioinformatics with GALEAS analysis software
Optimised for use with the GALEAS HereditaryPlus panel, our cloud-based bioinformatics pipelines deliver the accurate support consistent variant calling critical for reliable downstream data analysis including ALU repeats.
Optimised library preparation
GALEAS Heredytary PLUS library preparation is simple and easy compared to other targeted sequencing methods for hybridization and capture.
It requires as little as 10 ng of DNA and takes less than 10 hours, with less than two hours hands-on time. It is designed with multiple stop points to provide flexibility within laboratory processing. Library preparation can be run manually or automated (up to 96 samples in a single batch). Indexes are available for up to 384 samples to facilitate high throughput laboratories and to allow for flexible batch sizes.
Turnkey bioinformatics
Complimentary access to GALEAS cloud-based software delivers high quality variant calling for research purposes
Cutting-edge bioinformatics pipelines are included with purchases of GALEAS HereditaryPlus. GALEAS, our cloud-based software solution has been specifically tailored to work seamlessly with our NGS panels and optimized for secondary calling and comes with an in-built panel of normals to deliver optimum sensitivity for CNV calling.
All of this guarantees a robust and accurate analysis of germline variants critical to ensuring reliable downstream interpretation analysis and providing clinicians with reliable data to help them make informed decisions regarding personalized care and treatment strategies.
Cutting-edge bioinformatics pipelines were developed in tandem with, and specifically tailored for, GALEAS HereditaryPLUS kits to ensure optimal secondary calling.
As well as standard variant types SNV, INDEL , CNV and SV's. the software has also been shown to detect Boland inversions, BRCA2 and STK11 large deletions and AluY repeats.
This turn-key software solution comes with an in built panel of normals to deliver optimal sensitivity for CNV calling.
Requiring no specialist bioinformatic knowledge, GALEAS Hereditary plus analysis can be simply and easily integrated into research laboratories wishing to study hereditary cancer.
This software has not been validated for clinical diagnostic use.
Sequencing metrics for GALEAS HereditaryPlus
| Key quality indicator | GALEAS™ HereditaryPlus | Company I |
|---|---|---|
| Number of genes | 146 | 113 |
| Capture panel size (kb) | 809 | 403 |
| Mb required for mean 100x coverage | 130.0 Mb | 116.6 Mb |
| Percentage coverage >30x | 99.00% | 96.00% |
| Percentage on bait | 71.20% | 37.00% |
| Percentage on or near bait | 81.00% | 61.51% |
| Percent duplication | 2.00% | 8.99% |
| SNV recall | 99.70% | 98.10% |
| INDEL recall | 100.00% | 97.20% |
Poster presented at ESHG 2024
To assess assay performance in a research setting, it is often necessary to source multiple samples containing variants across different genes. This can be difficult and costly. This poster describes the use of GALEAS Hereditary Plus alongside two other assays for the evaluation of a prototype reference material. The data demonstrates identification of ALU and Boland inversion variants and illustrate the range of variants identified using GALEAS™ HereditaryPlus.
The GALEAS HereditaryPlus workflow is simple and easy
Wide range of sample types
DNA extraction
GALEAS HereditaryPlus
Illumina NGS sequencing system
GALEAS™ analysis software
Tertiary software for interpretation and reporting
References
1. Family history and inherited cancer genes. Cancer Research UK. Accessed July 2023. Full article
Interested in adding GALEAS™ HereditaryPlus?
RESEARCH USE ONLY DISCLAIMER
GALEAS HereditaryPlus (RUO) is intended for research purposes only. It is not intended for use in diagnostic procedures or for clinical decision-making. Performance characteristics for clinical diagnostic use have not been established. For diagnostic applications, please see our GALEAS HereditaryPlus (UKCA) product. GALEAS Hereditary Cancer Panel | Nonacus
For research use only. Not for use in diagnostic procedures.
