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Association details:
Biomarker:MAP2K1 mutation
Cancer:Ovarian Cancer
Drug:Koselugo (selumetinib) (MEK inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: C4 – Case Studies
New
Title:

Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

Excerpt:
Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor-based combination therapy.
DOI:
10.1200/JCO.2015.62.4726