What question did this study set out to answer?

To characterize the effects of mutant allele copy number gains in KRAS and other oncogenes across cancer types and assess their role in therapeutic response.

March 7, 2026Cancer Research

Abstract A050: Mutant allele copy number gains define distinct molecular subtypes of oncogene-driven cancers and are associated with response to allele-specific KRASG12C inhibitor sotorasib in NSCLC

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To characterize the effects of mutant allele copy number gains in KRAS and other oncogenes across cancer types and assess their role in therapeutic response.
Analyzed data from 33,473 cancer patients profiled by MSK-IMPACT.
Focused on 10,129 patients with oncogenic mutations in diploid tumors.
Inferred allele-specific copy number via FACETS and performed gene expression analysis using TCGA data.
Conducted drug screening for sotorasib in cell lines to evaluate sensitivity based on mutant dosage.
18% of all oncogene-mutated tumors exhibited mutant dosage gains, predominantly 1- or 2-copy.
Higher prevalence of KRAS mutant gains observed in metastatic tumors (27%) versus primary tumors (13%).
In KRAS G12C lung cancer, 57% of patients with dosage gains responded to sotorasib, compared to 17% without these gains.
Gene expression analysis showed higher KRAS expression correlating with increased dosage.

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Implication

Evaluates KRAS mutant dosage gains and their impact on therapeutic response in various cancers, suggesting key biomarkers for treatment efficacy.

Cite This Study

Perry et al. (2026) studied this question.

synapsesocial.com/papers/69abc1765af8044f7a4ea1df https://doi.org/10.1158/1538-7445.rasoncother26-a050

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Implication

Evaluates KRAS mutant dosage gains and their impact on therapeutic response in various cancers, suggesting key biomarkers for treatment efficacy.

Abstract A050: Mutant allele copy number gains define distinct molecular subtypes of oncogene-driven cancers and are associated with response to allele-specific KRASG12C inhibitor sotorasib in NSCLC

Key Points

Discussion

Implication

Cite This Study

Abstract A050: Mutant allele copy number gains define distinct molecular subtypes of oncogene-driven cancers and are associated with response to allele-specific KRASG12C inhibitor sotorasib in NSCLC

Key Points

Discussion

Implication

Cite This Study

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