Table 2.
Summary of compiled findings regarding mutation and expression of the cancer driver genes in endometriosis and fibrogenesis
| Gene | Chromosomal location | Role in tumorigenesis | Mutations reported in benign conditions | Mutation in endometriosis | Expression in endometriosis | Possible roles in fibrogenesis |
|---|---|---|---|---|---|---|
| TP53 | 17p13.1 | Tumor suppressor | Inactivating mutation in rheumatoid arthritis138, 139 | Found in adjacent to ovarian cancer,83 also loss.84Negative reports also. | Mixed results.Likely to be downregulated | TP53 loss suppress senescence of activated fibroblasts, promoting fibrogenesis |
| PTEN | 10q23.3 | Tumor suppressor | Inactivating,51One reports 21% in OMA147; Another reports 53% 148 | Reduced expression in endometriosis.151, 152, 153 | Activates the PI3K/AKT signaling pathway, suppresses the apoptosis of fibroblasts, and enhances their proliferation and invasiveness. Initiates SMAD3‐ and TP53‐dependent fibrotic response | |
| ARID1A | 1p36.11 | Tumor suppressor | Inactivating,51Partial or complete loss of expression,46 , 48 , 206 | Loss of ARID1A promotes wound regeneration | ||
| PIK3CA | 3q26.32 | Oncogene | Soborrheickeatosis: ~16%Fibroadipose hyperplasia: 90% | Activating, Also reported in the context of its link with ovarian cancer223, 224 | Activated PI3K/AKT/mTOR signaling pathway has been implicated190, 225, 226, 227, 228, 229 | Not documented. |
| KRAS | 12p12.1 | Oncogene | Activating51 | Upregulated in eutopic endometrium252, 253, 254 | Induction of ERK1/2 and in cooperation with Snail. | |
| PPP2AR1 | 19q13.41 | Oncogene | Activating 51 | NR | Impair PP2A activity | |
| ALK | 2p23.1 | Oncogene | Inflammatory myofibroblastic tumor: ~50%53 | NR | NR | Not well documented |
| BRAF | 7q34 | Protooncogene | Melanocytic nevi: 70‐88% 53 | NR | Overexpressed307 | Not well documented |
| CDKN2A | 9p21.3 | Tumor suppressor | LOH.85 Aberrant methylation151 |
Reduced expression of p16311; Likely to be low312 |
A marker for cellular senescence, which can restrict fibrogenesis | |
| FGFR3 | 4p16.3 | Oncogene | NR | NR | Not documented | |
| GNAQ | 9q21.2 | Oncogene | Sturge‐Weber syndrome: 88%53 | NR | NR | Not documented |
| NF1 | 17q11.2 | Tumor suppressor | Neurofibromas and pilocyticastrocytomas53 | only in endometriosis‐associated ovarian cancer282 | Reduced expression in OMA96 | Not well documented |
| NF2 | 22q12.2 | Tumor suppressor | Schwannomas, meningioma, glioma and ependymomaastrocytomas53 | NR | NR | Its suppression is likely to promote fibrogenesis through interaction with Hippo, TGFβ and Wnt‐β‐catenin pathways |
| NOTCH1 | 9q34.4 | Tumor‐suppressive and Oncogenic | Sun‐exposed skin53 | NR | Increased expression in peritoneum adjacent to endometriotic lesions354 | Facilitates FMT and fibrogenesis |
| NRAS | 1p13.2 | Oncogene | Melanocytic nevi: 6%‐14%53 | NR | Overexpressed307 | Not documented |
ALK, anaplastic lymphoma kinase; ARID1A, the AT‐rich interactive domain 1A; FGFR3, Fibroblast growth factor receptor 3; PTEN, phosphatase and tensin homolog deleted on chromosome 10; NF1, Neurofibromin 1; NF2, Neurofibromin 2; OMA, ovarian endometrioma; NR, not reported.