Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma
Abstract
:1. Introduction
2. Results
2.1. Enrichment of Secondary Mutations in G-Protein Related Pathways
2.2. Expression Analysis
2.3. PTK2B as a Secondary Driver Mutation
2.4. Signatures of Somatic Mutations in UM
3. Discussion
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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KEGG Pathway | # of Query Genes | # Total Annotated | p-Value | Adjusted p-Value | Genes |
---|---|---|---|---|---|
Aldosterone synthesis and secretion * | 41 | 98 | 1.38 × 10−6 | 3.79 × 10−4 | SCARB1, CAMK2D, ITPR1, ADCY4, ITPR2, ATP1A3, ADCY3, ATP1A2, CACNA1D, ITPR3, CACNA1C, CALML4, CACNA1F, CACNA1H, LIPE, CACNA1I, MC2R, PRKACG, CACNA1S, CAMK2G, PRKCG, KCNJ5, CAMK1D, HSD3B2, PRKCB, HSD3B1, ATP1B4, ATP2B2, PRKCA, AGT, NR4A2, POMC, PLCB3, AGTR1, PRKD2, CAMK1, PRKD1, PLCB1, DAGLB, PLCB2, ATF4 |
Calcium signaling pathway * | 66 | 188 | 2.48 × 10−6 | 3.79 × 10−4 | RYR1, RYR2, CHRM1, ATP2A3, ATP2A1, CALML4, RYR3, MYLK3, SLC8A1, MYLK, HTR6, GRM5, CCKAR, EDNRB, PRKACG, BDKRB1, PLCE1, NOS1, PDGFRB, PRKCG, PDGFRA, CAMK1D, PRKCB, SPHK1, PRKCA, ITPKB, PLCB3, ADORA2A, LTB4R2, ADORA2B, AGTR1, PLCB1, SLC25A5, PLCB2, CAMK2D, PDE1C, CACNA1B, ITPR1, ADCY4, ITPR2, ADCY3, CACNA1D, ITPR3, CACNA1C, CACNA1F, CACNA1E, EGFR, CACNA1H, CACNA1I, GRIN2A, ERBB4, PTK2B, CACNA1S, PLCG1, CAMK2G, NTSR1, NOS2, NOS3, ATP2B2, PHKB, TPCN2, TPCN1, GRIN2D, CAMK1, PLCD4, MCU |
Thyroid hormone signaling pathway | 45 | 116 | 5.08 × 10−6 | 5.17 × 10−4 | NOTCH2, NOTCH3, NOTCH1, HDAC1, ITGB3, SLC2A1, ATP1A3, ATP1A2, MED16, HIF1A, ACTB, SLC9A1, MED17, CASP9, MED12, MED14, MED13, MYC, PRKACG, EP300, PLCE1, PLCG1, SLC16A2, RXRG, PRKCG, NCOA2, CREBBP, PRKCB, ATP1B4, TSC2, SLC16A10, PRKCA, ESR1, MTOR, MED13L, BMP4, KAT2A, PLCB3, PIK3CA, CTNNB1, PLCB1, PLCD4, PLCB2, PFKP, MYH6 |
Ras-proximate-1 (RAP1) signaling pathway * | 67 | 206 | 3.69 × 10−5 | 2.87 × 10−3 | FLT4, ITGB3, CALML4, SIPA1L3, ACTB, IGF1R, FGF9, KDR, RAC2, RAC3, PLCE1, MAP2K3, MAGI1, PDGFRB, PRKCG, PDGFRA, PRKCB, ARAP3, PRKCA, NGF, VAV2, TIAM1, PLCB3, MRAS, ADORA2A, PIK3CA, ADORA2B, PARD3, KIT, RAPGEF2, PFN4, PRKD2, TLN2, PRKD1, PLCB1, PLCB2, MET, RAPGEF6, RGS14, GNAI3, ADCY4, FPR1, ADCY3, LPAR3, RASGRP2, THBS1, EGFR, GRIN2A, KRIT1, PLCG1, FGF23, NGFR, ANGPT4, EGF, VEGFB, GRIN2B, FGF17, EFNA2, FGF19, CTNNB1, TEK, FGFR4, FGFR2, LAT, SIPA1, FGFR1, FGF10 |
Protein digestion and absorption | 35 | 90 | 5.15 × 10−5 | 3.14 × 10−3 | COL17A1, COL18A1, PRSS1, CPB2, COL14A1, COL11A2, SLC1A1, ATP1A3, ATP1A2, SLC8A1, PRSS3, SLC36A1, CPA2, SLC6A19, SLC15A1, COL27A1, KCNJ13, COL22A1, ATP1B4, SLC16A10, COL1A1, SLC9A3, COL3A1, SLC7A7, COL2A1, COL5A1, COL4A2, COL4A1, XPNPEP2, MEP1A, COL5A3, COL5A2, COL4A3, COL9A1, COL9A2 |
Cortisol synthesis and secretion | 26 | 65 | 2.69 × 10−4 | 9.92 × 10−3 | SCARB1, ITPR1, ADCY4, ITPR2, ADCY3, CACNA1D, ITPR3, CACNA1C, CACNA1F, CACNA1H, CYP17A1, CACNA1I, MC2R, PRKACG, CACNA1S, PDE8B, PDE8A, HSD3B2, HSD3B1, AGT, POMC, PLCB3, AGTR1, PLCB1, PLCB2, ATF4 |
ATP-binding cassette ABC transporters | 20 | 45 | 2.59 × 10−4 | 9.92 × 10−3 | ABCA1, ABCA2, ABCC4, ABCD2, ABCC2, ABCB1, ABCB4, ABCC5, ABCA3, ABCA4, ABCC6, ABCA9, TAP2, ABCA7, ABCA12, ABCB11, ABCA13, ABCA10, ABCB10, ABCD1 |
Circadian entrainment * | 35 | 97 | 2.93 × 10−4 | 9.92 × 10−3 | RYR1, GRIA1, RYR2, CAMK2D, GNAI3, ITPR1, ADCY4, ADCY3, CACNA1D, ITPR3, CACNA1C, CALML4, RYR3, CACNA1H, CACNA1I, GRIN2A, RASD1, PRKACG, NOS1, CAMK2G, PRKG1, PRKCG, KCNJ5, PRKCB, PRKCA, GRIN2B, GRIN2D, PER1, PLCB3, GNB2, NOS1AP, GNB1, GNB3, PLCB1, PLCB2 |
Cushing syndrome | 51 | 155 | 2.15 × 10−4 | 9.92 × 10−3 | RB1, SCARB1, PRKACG, PDE8B, PDE8A, MEN1, USP8, AXIN1, AIP, PLCB3, AGTR1, PLCB1, PLCB2, ATF4, KMT2D, CAMK2D, KMT2A, TCF7, GNAI3, ITPR1, ADCY4, ITPR2, ADCY3, CACNA1D, ITPR3, CACNA1C, CACNA1F, EGFR, CACNA1H, CYP17A1, CACNA1I, PDE11A, MC2R, RASD1, DVL2, DVL3, CACNA1S, WNT2, CAMK2G, TCF7L2, WNT10A, TCF7L1, FZD2, HSD3B2, FZD5, WNT3A, HSD3B1, AGT, POMC, APC, CTNNB1 |
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Piaggio, F.; Tozzo, V.; Bernardi, C.; Croce, M.; Puzone, R.; Viaggi, S.; Patrone, S.; Barla, A.; Coviello, D.; J. Jager, M.; et al. Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma. Cancers 2019, 11, 1688. https://doi.org/10.3390/cancers11111688
Piaggio F, Tozzo V, Bernardi C, Croce M, Puzone R, Viaggi S, Patrone S, Barla A, Coviello D, J. Jager M, et al. Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma. Cancers. 2019; 11(11):1688. https://doi.org/10.3390/cancers11111688
Chicago/Turabian StylePiaggio, Francesca, Veronica Tozzo, Cinzia Bernardi, Michela Croce, Roberto Puzone, Silvia Viaggi, Serena Patrone, Annalisa Barla, Domenico Coviello, Martine J. Jager, and et al. 2019. "Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma" Cancers 11, no. 11: 1688. https://doi.org/10.3390/cancers11111688