GALEAS^TM Hereditary^Plus Features

Enhanced Clinically Relevant Content for Assessment of Hereditary Cancer Variants

Curation and coverage of 146 clinically significant genes associated with hereditary tumors, including breast cancer, prostate cancer, Lynch syndrome, and Wilms tumor.

Exceptional Accuracy and Reproducibility

Enhanced probe design, comprehensive coverage, and high uniformity allow for accurate and highly sensitive detection of SNVs, INDELs, and CNVs.

Supported by GALEAS™ Analysis Software

The dedicated, optimized cloud-based bioinformatics pipeline addresses various variants associated with hereditary tumors, delivering accurate results.

Panel Design

The panel is designed to target 146 genes associated with hereditary tumors. These genes encompass not only hereditary tumors such as breast and prostate cancers but also rare hereditary tumors like pheochromocytoma and Wilms tumor, which are often seen in pediatric cases (Table 1).

Additionally, careful curation ensures coverage of clinically significant areas, including non-coding regions such as the 5′ UTR of BRCA1/2 and the APC promoter.

When combined with the dedicated GALEAS™ analysis software, the panel enables the sensitive and specific detection of SNVs, INDELs, and CNVs.

Table 1 Genes included in key guidelines associated with risk of developing hereditary cancers and included in the GALEAS^TM Hereditary^Plus panel

GALEAS™ Hereditary^Plus Panel Performance

With exceptional accuracy and reproducibility, the system accurately detects SNVs and INDELs. Validation was performed on 437 SNPs using the commercially available standard control NA24385 (Table 2).

Table 2 GALEAS™ Hereditary^Plus SNV and indel recall across 4 replicates of reference standard NA24385

Superior Precision and Recall Ensure Confident Calling of Copy Number Variants (CNVs)

To evaluate the sensitivity of CNV genotyping, analyses were conducted using the NIBSC Lynch syndrome MLPA cell line. All CNVs were detected with 100% reproducibility and accuracy (Table 3).

Table 3 Recall and Precision Statistics for Copy Number Alterations (CNVs) in NIBSC Reference Controls Using the GALEAS™ Hereditary^Plus panel

Panel Performance Specifications

With a high percentage of on-target reads, low duplication rates, and more consistent vertical coverage, 99% of the targets are covered at 30x or greater (Table 4).

This outstanding technical performance enables a higher reproducibility and accuracy for a greater number of variants associated with hereditary cancers, including CNVs, while demonstrating superiority over leading competitors without significantly increasing sequencing costs.

Table 4 Sequencing Metrics for GALEAS™ Hereditary ^Plus. Compared with another commercial alternative, GALEAS™ Hereditary ^Plus delivers 100% more content (including CNV probes) for less than 10% more sequencing

Clinical Validation

The clinical utility of GALEAS™ Hereditary ^Plus was assessed using research collaborator samples, including gDNA from 64 patient blood samples.

SNV Recall and Precision

SNV recall on clinical samples was shown to be 100%, across a wide range of alteration types, including small and large (>10 bp) INDELS (Table 5).

Table 5 SNV Recall on Clinical Samples for GALEAS™ Hereditary ^Plus

Copy Number Variants (CNVs)

The combination of GALEAS™ Hereditary ^Plus which accurately identifies CNVs and GALEAS™ Analysis Software, it offers:

• Capability to deliver CNV detection in PMS2 (Figure 1C)
• Detection of a wide range of CNVs, from single exons to whole gene
• The ability to detect mosaic copy number variations in key genes such as APC and TSC2 (Figure 1E and F)

References

1. Ngeow J, Eng C. Precision medicine in heritable cancer: when somatic tumour testing and germline mutations meet. NPJ Genomic Medicine. 2016;(1):1-3.