Table 2.
Summary of PPM1D genetic amplification and mutations in solid cancers.
| Cancer type | PPM1D status | % | Prognosis (if available) and characteristics | Ref. |
|---|---|---|---|---|
| Ovarian | Amplification | 10% | Silencing of PPM1D in vitro led to reduced cell survival. | (22) |
| Breast | Amplification | 16% | Attenuation of apoptosis in vitro. Cooperated with RAS to transform primary MEFs. | (7) |
| Amplification | 11% | Associated with poor prognosis. | (4) | |
| Amplification | 6% | More prevalent in HER2+ breast cancers (19%) No association between PPM1D gene amplification or overexpression with disease-free, metastasis-free, or overall survival. | (20) | |
| Neuroblastoma | Amplification | 28% (9/32) | High expression of PPM1D correlated with significantly worse survival outcomes. | (54) |
| Medulloblastoma | Amplification and overexpression | 64% | Increased PPM1D expression associated with metastasis and decreased survival. Associated with CXCR4 and GRK5 upregulation. | (51, 55, 83) |
| Pancreatic adenocarcinoma | Amplification | 51% (86/169) | 43% had metastatic disease at follow-up and harbored at least one mutation in MDM2, MDM4, or WIP1. | (23) |
| Overexpression | 55% | PPM1D expression positively correlated with tumor grade; promotes cell migration and invasion in vitro and tumor growth in vivo. | (94) | |
| Colorectal | Overexpression | 68% (252/368) | PPM1D expression significantly increased in tumors with nodal and distant metastasis and advanced TNM stages. | (14) |
| Papillary thyroid | Overexpression | 63% (56/89) | PPM1D expression positively correlated with tumor size and lymph node metastasis. | (84) |
| Prostate cancer | Overexpression | 56.4% (132/234) | PPM1D expression positively correlated with Gleason score, T-stage, lymph node status, and shorter biochemical recurrence-free survival, and decreased overall survival. | (15) |
| Salivary carcinoma | Overexpression | 100% (82/82) | Correlated with malignant disease and poor prognosis. | (57) |
| Non--small cell lung cancer | Overexpression | 69% (52/75) | Positively correlated with clinical stage, lymph node metastasis, and pathologic differentiation. | (16) |
| Nasopharyngeal carcinoma | Overexpression | Unclear | Positively correlated with advanced clinical stage, lymph node metastasis, response to ionizing radiation; poor 5-year survival. | (58) |
| Renal cell carcinoma | Overexpression | 68% (53/78) | Positively correlated with T stages, lymph node metastasis, clinical stages and tumor differentiation, with poor overall survival. | (60) |
| Esophageal squamous cell carcinoma | Overexpression | 69% (70/101) | Poor prognosis, lymph node metastasis, inferior 5-year survival. | (53) |
| Osteosarcoma | Overexpression | 51% (23/45) | Higher levels of PPM1D detected in patients with distant metastasis and unfavorable prognosis. | (59) |
| Glioma | Truncating mutation | 23% (3/13) 18% | PPM1D mutations mutually exclusive with TP53 mutations but always found in conjunction with NF1 mutations and frequently with H3F3A. | (8,46) |