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NPJ Genom Med. 2017 Jul 6;2:22. doi: 10.1038/s41525-017-0025-4. eCollection 2017.

Mosaic mutations in blood DNA sequence are associated with solid tumor cancers.

Author information

Broad Institute, Cambridge, MA 02139 USA.
Analytic and Translational Genetics Unit, MGH, Boston, MA 02114 USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138 USA.
Department of Biomedical Data Science, Stanford University, Stanford, CA 94305 USA.


Recent understanding of the causal role of blood-detectable somatic protein-truncating DNA variants in leukemia prompts questions about the generalizability of such observations across cancer types. We used the cancer genome atlas exome sequencing (~8000 samples) to compare 22 different cancer phenotypes with more than 6000 controls using a case-control study design and demonstrate that mosaic protein truncating variants in these genes are also associated with solid-tumor cancers. The absence of these cancer-associated mosaic variants from the tumors themselves suggest these are not themselves tumor drivers. Through analysis of different cancer phenotypes we observe gene-specificity for mosaic mutations. We confirm a specific link between PPM1D and ovarian cancer, consistent with previous reports linking PPM1D to breast and ovarian cancer. Additionally, glioblastoma, melanoma and lung cancers show gene specific burdens of mosaic protein truncating mutations. Taken together, these results extend existing observations and broadly link solid-tumor cancers to somatic blood DNA changes.

Conflict of interest statement

The authors declare no competing financial interests.

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