The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond
Abstract
:Simple Summary
Abstract
1. Introduction
2. MRN Complex Functions in Cellular Homeostasis
2.1. MRN Complex in DSBs and Replication Stress Handling
2.1.1. MRN Complex Defects as Risk Factor for Cancer Development and Assumption for a Synthetic Lethal-Based Strategy
2.1.2. MRN Complex as a Critical Factor in Resistance to Oncogene- and Therapy-Induced DSBs/RS
2.2. MRN Complex in Innate and Adaptive Immune Response
2.3. MRN Complex in Telomere Homeostasis
2.4. MRN Complex in Centrosome Maintenance and Mitotic Spindle Dynamic
2.5. MRN Complex and Cancer-Related Pathways
3. The Prognostic Significance of the MRN Complex Expression in Cancer
4. Medulloblastoma as a Model for the Pleiotropic Role of MRN Complex in Cancer
5. Future Perspective/Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cancer | Mutation | Number of Patients with Cancer | % of Cancer Patients with NBN Mutation | Number of Healthy Subjects | % of Healthy Subjects with NBN Mutation | Statistical Analysis | PubMed IDentifier |
---|---|---|---|---|---|---|---|
Acute Lymphoblastic Leukaemia | p.I171V | 46 | 10.7 | 2400 | 0.5 | 0.0004 | 24093751 |
Acute myeloid leukemia | p.I171V | 32 | 6.3 | 2400 | 0.5 | 0.0001 | 24093751 |
Breast (familial) | c.657_661del5 | 80 | 1.3 | 530 | 0.6 | n.s | 12845677 |
Breast | c.657_661del5 | 173 | 1.2 | 344 | 0 | 0.046 | 15578693 |
c.657_661del5 | 224 | 1.8 | 1620 | 0.6 | n.s. | 15185344 | |
c.657_661del5 | 150 | 3.7 | 530 | 0.6 | 0.037 | 12845677 | |
c.657_661del5 | 562 | 2.0 | 1620 | 0.6 | 0.0107 | 16770759 | |
c.657_661del5 | 700 | 0.7 | 344 | 0 | n.s. | 15578693 | |
Colorectal | c.657_661del5 | 234 | 1.3 | 1620 | 0.6 | n.s. | 15185344 |
I171V | 131 | 2.3 | 600 | 0.2 | 0.0196 | 18280732 | |
IVS11+2insT | 472 | 0.6 | 2348 | 0.08 | 0.02 | 18056440 | |
R215W | 234 | 1.3 | 1620 | 0.2 | 0.0472 | 15185344 | |
Gastric cancer | IVS11+2insT | 472 | 0.4 | 2348 | 0.08 | 0.0001 | 18056440 |
Gastrointestinal lymphoma | c.657_661del5 | 37 | 10.8 | 1620 | 0.6 | 0.0002 | 16998789 |
Head and neck | I171V | 81 | 6.2 | 600 | 0.2 | 0.0001 | 18280732 |
Larynx cancer | I171V | 176 | 2.3 | 500 | 0.2 | 0.0175 | 17894553 |
Lung | c.551A>G | 453 | 3.8 | 2400 | 0.5 | <0.0001 | 26722329 |
c.657_661del5 | 453 | 0.7 | 2090 | 0.2 | n.s. | 26722329 | |
IVS11+2insT | 532 | 0.4 | 2348 | 0.08 | n.s. | 18056440 | |
Medulloblastoma | c.511A>G | 104 | 3.8 | 4227 | 1.3 | 0.0241 | 19908051 |
c.657_661del5 | 104 | 2.9 | 12,484 | 0.6 | 0.0028 | 19908051 | |
Melanoma | c.657_661del5 | 376 | 0.3 | 866 | 0.1 | n.s. | 17496786 |
c.657_661del5 | 80 | 2.5 | 530 | 0.6 | n.s. | 12883362 | |
c.657_661del5 | 105 | 3.8 | 1620 | 0.6 | 0.0081 | 15185344 | |
Non-Hodgkin Lymphoma | c.657_661del5 | 109 | 0 | 984 | 0.3 | n.s. | 10848790 |
c.657_661del5 | 42 | 4.8 | 1620 | 0.6 | 0.0351 | 15185344 | |
c.657_661del5 | 228 | 3.5 | 1620 | 0.6 | 0.0001 | 16998789 | |
Prostate (familial) | c.657_661del5 | 56 | 9.0 | 1500 | 0.60 | <0.0001 | 14973119 |
Prostate | c.657_661del5 | 305 | 2.2 | 1500 | 0.60 | 0.01 | 14973119 |
Cancer | Mutation | Number of Patients with Cancer | % of Cancer Patients with RAD50 Mutation | Number of Healthy Subjects | % of Healthy Subjects with RAD50 Mutation | Statistical Analysis | PubMed IDentifier |
---|---|---|---|---|---|---|---|
Acute Lymphoblastic Leukaemia + Acute myeloid leukemia | - | 220 | - | 504 | 0.006 | 0.0019 | 24093751 |
Breast | 687delT | 317 | 2.52 | 1000 | 0.6 | 0.008 | 16474176 |
- | 7657 | 0.07 | 5000 | 0.02 | n.s. | 29726012 | |
687delT | 590 | 0.5 | 560 | 0.2 | n.s. | 16385572 | |
Breast/Ovarian | 687delT | 151 | 1.3 | 1000 | 0.6 | n.d. | 14684699 |
Esophageal squamous cell carcinoma | p.K722fs | 2088 | 0.14 | 2342 | 0 | 0.032 | 34572942 |
p.Q672X/p.K722fs | 2088 | 0.19 | 2342 | 0 | 0.01 | 34572942 | |
FH+ Esophageal squamous cell carcinoma | - | 372 | 1.1 | 19,954 | 0.15 | 0.0033 | 34572942 |
Cancer | Mutation | Number of Patients with Cancer | % of Cancer Patients with MRE11 Mutation | Number of Healthy Subjects | % of Healthy Subjects with MRE11 Mutation | Statistical Analysis | PubMed IDentifier |
---|---|---|---|---|---|---|---|
Breast | - | 75,818 | 0.05 | 111,326 | 0.05 | n.s. | 31406321 |
p.E506 * | 1925 | 0 | 2287 | 0.002 | n.s. | 33510186 | |
p.R364X | 1 | n.d. | 100 | 0 | n.d. | 28559769 | |
Colorectal | - | 1006 | 0.3 | 1609 | 0 | n.d. | 27329137 |
- | 49 | 0.84 | n.d. | n.d. | n.d. | 15048091 | |
Endometrium | - | 14 | 7 | n.d. | n.d. | n.d. | 15048091 |
p.E506 * | 367 | 0 | 2287 | 0.002 | n.s. | 33510186 | |
Gastric MSI | poly(T)11 | 27 | 0.81 | n.d. | n.d. | n.d. | 15319296 |
Hereditary Breast and Ovarian Cancer | p.R305W | 151 | 0.3 | 1000 | 0 | n.d. | 14684699 |
- | 708 | 0.4 | n.d. | n.d. | n.d. | 24549055 | |
Medulloblastoma MSI | poly(T)11 | 4 | 0.25 | n.d. | n.d. | n.d. | 19179424 |
Ovary | p.E506 * | 341 | 0 | 2287 | 0.002 | n.s. | 33510186 |
- | 5 | 0.2 | n.d. | n.d. | n.d. | 15048091 | |
Stomach | - | 1 | 1.0 | n.d. | n.d. | n.d. | 15048091 |
Ureter | - | 1 | 0 | n.d. | n.d. | n.d. | 15048091 |
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Petroni, M.; La Monica, V.; Fabretti, F.; Augusto, M.; Battaglini, D.; Polonara, F.; Di Giulio, S.; Giannini, G. The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond. Cancers 2023, 15, 3599. https://doi.org/10.3390/cancers15143599
Petroni M, La Monica V, Fabretti F, Augusto M, Battaglini D, Polonara F, Di Giulio S, Giannini G. The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond. Cancers. 2023; 15(14):3599. https://doi.org/10.3390/cancers15143599
Chicago/Turabian StylePetroni, Marialaura, Veronica La Monica, Francesca Fabretti, Mariaconcetta Augusto, Damiana Battaglini, Francesca Polonara, Stefano Di Giulio, and Giuseppe Giannini. 2023. "The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond" Cancers 15, no. 14: 3599. https://doi.org/10.3390/cancers15143599
APA StylePetroni, M., La Monica, V., Fabretti, F., Augusto, M., Battaglini, D., Polonara, F., Di Giulio, S., & Giannini, G. (2023). The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond. Cancers, 15(14), 3599. https://doi.org/10.3390/cancers15143599