Computational analysis of pathways affected by proviral insertions
| Pathways . | Genes . | P . |
|---|---|---|
| Ingenuity pathways | ||
| VEGF signaling | Rras2, Vcl*, Bcl2*, Raf1*, Kdr, Plcg2* | < .001 |
| <G1/S checkpoint regulation | Myc2, Ccnd1, Ccnd22, Hdac6, E2f2 | < .001 |
| ERK/MAPK signaling | Rras2, Myc2, Raf1*, Prkar2b*, Mycn, Ets12, Plcg2* | < .001 |
| B-cell receptor signaling | Pou2f2, Rras2, Vav32*, Raf1*, Ets12, Plcg2* | < .001 |
| T-cell receptor signaling | Rras2, Vav32*, Raf1*, Rasgrp14, Itk2 | < .001 |
| GM-CSF signaling | Rras2, Ccnd1, Raf1*, Ets12 | < .001 |
| PDGF signaling | Rras2, Myc2, Raf1*, Plcg2* | .001 |
| Leukocyte extravasation signaling | Vav32*, Pecam1, Vcl*, Itk2, Mmp14, Plcg2* | .001 |
| Neuregulin signaling | Rras2, Myc2, Raf1*, Plcg2* | .002 |
| FcϵRI signaling | Rras2, Vav32*, Raf1*, Plcg2* | .004 |
| PTEN signaling | Rras2, Bcl2*, Ccnd1, Raf1* | .005 |
| Apoptosis signaling | Rras2, Bcl2*, Raf1*, Plcg2* | .006 |
| Natural killer cell signaling | Rras2, Vav32*, Raf1*, Plcg2* | .006 |
| JAK/Stat signaling | Socs6*, Rras2, Raf1* | .007 |
| G-protein–coupled receptor signaling | Pde1a*, Rras2, Raf1*, Prkar2b*, Rasgrp14 | .011 |
| PI3K/AKT signaling | Rras2, Bcl2*, Ccnd1, Raf1* | .013 |
| N-glycan biosynthesis | Rpn1*, Dpagt1*, Mgat4a* | .015 |
| Chemokine signaling | Rras2, Raf1*, Plcg2* | .018 |
| IGF-1 signaling | Rras2, Raf1*, Prkar2b* | .02 |
| Actin cytoskeleton signaling | Arhgef6*, Rras2, Vav32*, Vcl*, Raf1* | .021 |
| p38 MAPK signaling | Myc2, Map3k7ip2*, Mef2c3 | .025 |
| Estrogen receptor signaling | Rras2, Raf1*, Crsp2* | .035 |
| Synaptic long-term potentiation | Rras2, Raf1*, Prkar2b* | .04 |
| KEGG pathways | ||
| Dorsal-ventral axis formation | Rras2, Ets1, Notch13, Raf1* | .005 |
| Jak-STAT signaling | Ccnd1, Il12a*, Myc2, Mpl*, Ccnd22, Il21r*, Socs6* | .007 |
| Focal adhesion | Ccdn1, Vav32*, Rras2, Vcl*, Kdr, Ccnd22, Bcl2*, Raf1* | .011 |
| T-cell receptor signaling | Icos*, Vav32*, Rras2, Rasgrp14, Itk2 | .026 |
| Leukocyte transendothelial migration | Plcg2*, Vav32*, Vcl*, Pecam1, Itk2 | .049 |
| Pathways . | Genes . | P . |
|---|---|---|
| Ingenuity pathways | ||
| VEGF signaling | Rras2, Vcl*, Bcl2*, Raf1*, Kdr, Plcg2* | < .001 |
| <G1/S checkpoint regulation | Myc2, Ccnd1, Ccnd22, Hdac6, E2f2 | < .001 |
| ERK/MAPK signaling | Rras2, Myc2, Raf1*, Prkar2b*, Mycn, Ets12, Plcg2* | < .001 |
| B-cell receptor signaling | Pou2f2, Rras2, Vav32*, Raf1*, Ets12, Plcg2* | < .001 |
| T-cell receptor signaling | Rras2, Vav32*, Raf1*, Rasgrp14, Itk2 | < .001 |
| GM-CSF signaling | Rras2, Ccnd1, Raf1*, Ets12 | < .001 |
| PDGF signaling | Rras2, Myc2, Raf1*, Plcg2* | .001 |
| Leukocyte extravasation signaling | Vav32*, Pecam1, Vcl*, Itk2, Mmp14, Plcg2* | .001 |
| Neuregulin signaling | Rras2, Myc2, Raf1*, Plcg2* | .002 |
| FcϵRI signaling | Rras2, Vav32*, Raf1*, Plcg2* | .004 |
| PTEN signaling | Rras2, Bcl2*, Ccnd1, Raf1* | .005 |
| Apoptosis signaling | Rras2, Bcl2*, Raf1*, Plcg2* | .006 |
| Natural killer cell signaling | Rras2, Vav32*, Raf1*, Plcg2* | .006 |
| JAK/Stat signaling | Socs6*, Rras2, Raf1* | .007 |
| G-protein–coupled receptor signaling | Pde1a*, Rras2, Raf1*, Prkar2b*, Rasgrp14 | .011 |
| PI3K/AKT signaling | Rras2, Bcl2*, Ccnd1, Raf1* | .013 |
| N-glycan biosynthesis | Rpn1*, Dpagt1*, Mgat4a* | .015 |
| Chemokine signaling | Rras2, Raf1*, Plcg2* | .018 |
| IGF-1 signaling | Rras2, Raf1*, Prkar2b* | .02 |
| Actin cytoskeleton signaling | Arhgef6*, Rras2, Vav32*, Vcl*, Raf1* | .021 |
| p38 MAPK signaling | Myc2, Map3k7ip2*, Mef2c3 | .025 |
| Estrogen receptor signaling | Rras2, Raf1*, Crsp2* | .035 |
| Synaptic long-term potentiation | Rras2, Raf1*, Prkar2b* | .04 |
| KEGG pathways | ||
| Dorsal-ventral axis formation | Rras2, Ets1, Notch13, Raf1* | .005 |
| Jak-STAT signaling | Ccnd1, Il12a*, Myc2, Mpl*, Ccnd22, Il21r*, Socs6* | .007 |
| Focal adhesion | Ccdn1, Vav32*, Rras2, Vcl*, Kdr, Ccnd22, Bcl2*, Raf1* | .011 |
| T-cell receptor signaling | Icos*, Vav32*, Rras2, Rasgrp14, Itk2 | .026 |
| Leukocyte transendothelial migration | Plcg2*, Vav32*, Vcl*, Pecam1, Itk2 | .049 |
The 168 RISs (out of 182) for which we have obtained accession numbers were subjected to pathway analysis using the Ingenuity and NIH-DAVID software packages. These software packages returned Ingenuity pathways and KEGG pathways, respectively. Only pathways with 3 proviral insertions in 3 or more genes are depicted. Pathways are sorted based on significance (cut-off, P < .05). A total of 32 (of 59) tumors are represented in one or more pathways. RISs affected in more than one tumor are depicted in bold, and the number of integrations is depicted in superscript. Please note that the NIH-DAVID software does not take into account multiple hits in individual genes.
Genes that are not defined as CISs in the RTCGD.