A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity

Grabiner BC, Nardi V, Birsoy K, Possemato R, Shen K, Sinha S, Jordan A, Beck AH, Sabatini DM · 2014 · Cancer discovery · Atlas ID GRA2014

What this study shows

A spectrum of cancer-associated MTOR mutations are hyperactivating and predict rapamycin sensitivity.

Abstract

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Genes encoding components of the PI3K-AKT-mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Cancer cell panels) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Cancer cell panels
Journal	Cancer discovery
Year	2014
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1158/2159-8290.CD-13-0929 · PMID 24631838 · Free full text (PMC4012430)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Genomics (MTOR mutations)
Target	mTOR (hyperactivating mutations)
Model	Cancer cell panels
Effect	Catalogs 33 hyperactivating cancer-associated MTOR mutations (6 clusters) that can predict rapamycin sensitivity

In the Atlas

Cite this paper

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Grabiner, B. C., Nardi, V., Birsoy, K., Possemato, R., Shen, K., Sinha, S., Jordan, A., Beck, A. H., & Sabatini, D. M. (2014). A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer discovery. https://doi.org/10.1158/2159-8290.CD-13-0929

@article{GRA2014,
  author       = {Grabiner, B. C. and Nardi, V. and Birsoy, K. and Possemato, R. and Shen, K. and Sinha, S. and Jordan, A. and Beck, A. H. and Sabatini, D. M.},
  title        = {{A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity}},
  journal      = {Cancer discovery},
  year         = {2014},
  doi          = {10.1158/2159-8290.CD-13-0929},
  note         = {PMID: 24631838},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GRA2014) [Data set]. https://mtor-atlas.org/study/GRA2014/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GRA2014,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GRA2014},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GRA2014/},
  doi          = {10.5281/zenodo.22059963}
}

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