PT  - JOURNAL ARTICLE
AU  - Mykyta Artomov
AU  - Manuel A. Rivas
AU  - Giulio Genovese
AU  - Mark J. Daly
TI  - Mosaic Mutations in Blood DNA Sequence Are Associated with Solid Tumor Cancers
AID  - 10.1101/065821
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 065821
4099  - http://biorxiv.org/content/early/2016/07/25/065821.short
4100  - http://biorxiv.org/content/early/2016/07/25/065821.full
AB  - Recent findings in understanding of the causal role of blood mosaic protein-truncating DNA variants in leukemia rose a question about generalizability of such observations for other cancer types. We used exome sequencing to compare 22 different cancer phenotypes from TCGA data (~8,000 samples) with more than 6,000 controls using a case-control study design and demonstrate that mosaic protein truncating variants in these genes are also associated with solid-tumor cancers. We analyzed tumor DNA samples from TCGA and observed that mosaic variants driving the association with cancer are absent from the tumors. By analysis of the different cancer phenotypes we observe gene-specificity for mosaic mutations. PPM1D in previous reports has been linked to breast and ovarian cancer, which our analysis confirms as a specific gene for ovarian cancer. Also glioblastoma, melanoma and lung cancers show gene specific burden of the mosaic protein truncating mutations. Taken together, these results represent an important observation of solid-tumor cancers being linked to the somatic blood DNA changes.