MEMo (Mutual Exclusivity Modules in Cancer)

Overview

MEMo (Mutual Exclusivity Modules in Cancer) is a computational method for identifying mutually exclusive patterns of genomic alterations across cancer samples. The algorithm searches for sets of genes that are altered in largely non-overlapping subsets of tumors, which is interpreted as evidence that the genes function in the same biological pathway (since co-mutation of pathway members provides no selective advantage). MEMo integrates mutation, copy-number, and epigenetic alteration data to identify pathway-level mutual exclusivity.

Used by

  • Applied in the TCGA GBM 2013 study to test mutual exclusivity across 291 GBM exomes; identified significant mutual exclusivity among chromatin modification gene (CMG) mutations (p=0.0008 across 135/291 samples with ≥1 CMG mutation), PI3K mutations vs. PTEN alterations (p=0.0047), and TP53 mutation vs. MDM amplification (p=0.0003) PMID:24120142
  • Applied in TCGA PTC study to confirm mutual exclusivity of MAPK-pathway drivers (BRAF + NRAS + HRAS + KRAS in 300/402 tumors; MEMo-corrected P<0.01) and to test mutual exclusivity among DNA-repair-related mutations PMID:25417114
  • Applied in the TCGA breast cancer ILC/IDC study to identify mutually exclusive oncogenic network alterations (MEMo analysis); identified AKT/mTOR pathway convergence in 45% of ILC samples via upstream RTK, PTEN, and PIK3CA alterations, with ~40% carrying upstream pathway events PMID:26451490

Notes

  • MEMo was developed at Memorial Sloan Kettering and Weill Cornell Medicine; published alongside cBioPortal.
  • The mutual exclusivity test accounts for alteration frequency and sample size to compute statistical significance.
  • Identification of mutual exclusivity supports pathway-level models of oncogenesis and helps delineate functional redundancy between genomic lesions.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

This page was processed by crosslinker on 2026-05-14.