MSK-ACCESS V1

Things to know for MSK-ACCESS V1 for Research

What is MSK-ACCESS?

It is a hybrid capture panel designed for Analysis of Circulating cfDNA to Evaluate Somatic Status using the Unique Molecular Index (UMIs) for high sensitivity. MSK-ACCESS is 13% as large, captures 47% of all mutations detected by MSK-IMPACT.

Brannon, A. R. et al. Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell- free DNA via paired normal sequencing using MSK-ACCESS. Nat Commun 12, 3770 (2021).

Duplex UMIs for Error Correction

What is the panel design?

Selected exons of 129 genes for mutation detection

• OncoKB Level 1-4
• Hotspot sites
• High rates of mutations

• Protein kinase domains
• Tumor suppressor genes

Microsatellite regions

SNPs of zygosity & copy number of 12 genes

Common SNPs for genome-wide copy number

Introns for structural variants of 10 genes

Clonal hematopoiesis genes

What are the Design Implications?

• Matched cfDNA-WBC (”tumor-normal”) assay to detect somatic alterations

• Sensitivity for mutation calling depends on ‘duplex’ collapsed coverage

• Different sensitivities for different classes of alterations

  • Genotyping +++++

  • De novo mutations, indels ++++

  • MSI +++

  • Rearrangements +++

  • Copy number ++

  • Tumor mutation burden ○

+ -> sensitivity for that event type

○ -> cannot be calculated