- Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China;
ZHENG Jinghao,
Email: zhengjh210@163.com
Primary cardiac tumors, which originate from the heart, are uncommon and can be classified as benign or malignant, with the majority being benign. Malignant primary cardiac tumors have a poor prognosis. Benign ones may also cause severe hemodynamic and electrophysiological consequences, but the prognosis is generally good if they are detected early and treated properly. In recent years, researches on the genetic and molecular causes of primary cardiac tumors have yielded some promising breakthroughs, with some of them already being translated into clinical practice. This article reviews research progress and its use in precise diagnosis and targeted therapy from the perspective of DNA, RNA, and protein changes, as well as prospects the promising research directions in the future.
Citation： CUI Yue, ZHENG Jinghao. Research advances in genetics and molecular biology of primary cardiac tumors. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(12): 1784-1790. doi: 10.7507/1007-4848.202203030 Copy
| 1. | Burke A, Tavora F. The 2015 WHO classification of tumors of the heart and pericardium. J Thorac Oncol, 2016, 11(4): 441-452. |
| 2. | Poterucha TJ, Kochav J, O'Connor DS, et al. Cardiac tumors: Clinical presentation, diagnosis, and management. Curr Treat Options Oncol, 2019, 20(8): 66. |
| 3. | Maleszewski JJ, Anavekar NS, Moynihan TJ, et al. Pathology, imaging, and treatment of cardiac tumours. Nat Rev Cardiol, 2017, 14(9): 536-549. |
| 4. | Bussani R, Castrichini M, Restivo L, et al. Cardiac tumors: Diagnosis, prognosis, and treatment. Curr Cardiol Rep, 2020, 22(12): 169. |
| 5. | Garatti A, Nano G, Canziani A, et al. Surgical excision of cardiac myxomas: Twenty years experience at a single institution. Ann Thorac Surg, 2012, 93(3): 825-831. |
| 6. | Paraskevaidis IA, Michalakeas CA, Papadopoulos CH, et al. Cardiac tumors. ISRN Oncol, 2011, 2011: 208929. |
| 7. | Jain D, Maleszewski JJ, Halushka MK. Benign cardiac tumors and tumorlike conditions. Ann Diagn Pathol, 2010, 14(3): 215-230. |
| 8. | Velez Torres JM, Martinez Duarte E, Diaz-Perez JA, et al. Cardiac myxoma: Review and update of contemporary immunohistochemical markers and molecular pathology. Adv Anat Pathol, 2020, 27(6): 380-384. |
| 9. | Samanidis G, Khoury M, Balanika M, et al. Current challenges in the diagnosis and treatment of cardiac myxoma. Kardiol Pol, 2020, 78(4): 269-277. |
| 10. | Campisi A, Ciarrocchi AP, Asadi N, et al. Primary and secondary cardiac tumors: Clinical presentation, diagnosis, surgical treatment, and results. Gen Thorac Cardiovasc Surg, 2022, 70(2): 107-115. |
| 11. | Paraf F. Pathology of primary cardiac tumors. Ann Pathol, 2021, 41(1): 50-57. |
| 12. | Teng F, Yang S, Chen D, et al. Cardiac fibroma: A clinicopathologic study of a series of 12 cases. Cardiovasc Pathol, 2022, 56: 107381. |
| 13. | Cresti A, Chiavarelli M, Glauber M, et al. Incidence rate of primary cardiac tumors: A 14-year population study. J Cardiovasc Med (Hagerstown), 2016, 17(1): 37-43. |
| 14. | Neuville A, Collin F, Bruneval P, et al. Intimal sarcoma is the most frequent primary cardiac sarcoma: Clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas. Am J Surg Pathol, 2014, 38(4): 461-469. |
| 15. | Joshi M, Kumar S, Noshirwani A, et al. The current management of cardiac tumours: A comprehensive literature review. Braz J Cardiovasc Surg, 2020, 35(5): 770-780. |
| 16. | Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: Diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab, 2001, 86(9): 4041-4046. |
| 17. | Groussin L, Horvath A, Jullian E, et al. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab, 2006, 91(5): 1943-1949. |
| 18. | Forlino A, Vetro A, Garavelli L, et al. PRKACB and Carney complex. N Engl J Med, 2014, 370(11): 1065-1067. |
| 19. | Bouys L, Bertherat J. Management of endocrine disease: Carney complex: Clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene. Eur J Endocrinol, 2021, 184(3): R99-R109. |
| 20. | Tseng IC, Huang WJ, Jhuang YL, et al. Microinsertions in PRKACA cause activation of the protein kinase A pathway in cardiac myxoma. J Pathol, 2017, 242(2): 134-139. |
| 21. | Hinton RB, Prakash A, Romp RL, et al. Cardiovascular manifestations of tuberous sclerosis complex and summary of the revised diagnostic criteria and surveillance and management recommendations from the International Tuberous Sclerosis Consensus Group. J Am Heart Assoc, 2014, 3(6): e001493. |
| 22. | Peron A, Au KS, Northrup H. Genetics, genomics, and genotype-phenotype correlations of TSC: Insights for clinical practice. Am J Med Genet C Semin Med Genet, 2018, 178(3): 281-290. |
| 23. | van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 1997, 277(5327): 805-808. |
| 24. | European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell, 1993, 75(7): 1305-1315. |
| 25. | Dibble CC, Elis W, Menon S, et al. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell, 2012, 47(4): 535-546. |
| 26. | Salussolia CL, Klonowska K, Kwiatkowski DJ, et al. Genetic etiologies, diagnosis, and treatment of tuberous sclerosis complex. Annu Rev Genomics Hum Genet, 2019, 20: 217-240. |
| 27. | Dragoumi P, O'Callaghan F, Zafeiriou DI. Diagnosis of tuberous sclerosis complex in the fetus. Eur J Paediatr Neurol, 2018, 22(6): 1027-1034. |
| 28. | Lee E, Mahani MG, Lu JC, et al. Primary cardiac tumors associated with genetic syndromes: A comprehensive review. Pediatr Radiol, 2018, 48(2): 156-164. |
| 29. | Onodera S, Nakamura Y, Azuma T. Gorlin syndrome: Recent advances in genetic testing and molecular and cellular biological research. Int J Mol Sci, 2020, 21(20): 7559. |
| 30. | Fu X, Niu W, Li J, et al. Activating mutation of PDGFRB gene in a rare cardiac undifferentiated intimal sarcoma of the left atrium: A case report. Oncotarget, 2017, 8(46): 81709-81716. |
| 31. | Ito Y, Maeda D, Yoshida M, et al. Cardiac intimal sarcoma with PDGFRβ mutation and co-amplification of PDGFRα and MDM2: An autopsy case analyzed by whole-exome sequencing. Virchows Arch, 2017, 471(3): 423-428. |
| 32. | Salvador-Coloma C, Saigí M, Díaz-Beveridge R, et al. Identification of actionable genetic targets in primary cardiac sarcomas. Onco Targets Ther, 2019, 12: 9265-9275. |
| 33. | Leduc C, Jenkins SM, Sukov WR, et al. Cardiac angiosarcoma: Histopathologic, immunohistochemical, and cytogenetic analysis of 10 cases. Hum Pathol, 2017, 60: 199-207. |
| 34. | Yan L, Li J, Wu Q, et al. Specific miRNA expression profile in the blood serum of cardiac myxoma patients. Oncol Lett, 2018, 16(4): 4235-4242. |
| 35. | Zhang J, Wang C, Xu H. miR-217 suppresses proliferation and promotes apoptosis in cardiac myxoma by targeting interleukin-6. Biochem Biophys Res Commun, 2017, 490(3): 713-718. |
| 36. | Cao Q, Dong P, Wang Y, et al. miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D. Oncol Rep, 2015, 33(5): 2606-2612. |
| 37. | Qiu Y, Yang J, Bian S, et al. PPARγ suppresses the proliferation of cardiac myxoma cells through downregulation of MEF2D in a miR-122-dependent manner. Biochem Biophys Res Commun, 2016, 474(3): 560-565. |
| 38. | Cheng N, Wu Y, Zhang H, et al. Identify the critical protein-coding genes and long noncoding RNAs in cardiac myxoma. J Cell Biochem, 2019, 120(8): 13441-13452. |
| 39. | Shiohama T, Fujii K, Miyashita T, et al. MicroRNAs profiling in fibroblasts derived from patients with Gorlin syndrome. J Hum Genet, 2019, 64(8): 757-765. |
| 40. | Pucci A, Mattioli C, Matteucci M, et al. Cell differentiation in cardiac myxomas: Confocal microscopy and gene expression analysis after laser capture microdissection. Heart Vessels, 2018, 33(11): 1403-1410. |
| 41. | Scalise M, Torella M, Marino F, et al. Atrial myxomas arise from multipotent cardiac stem cells. Eur Heart J, 2020, 41(45): 4332-4345. |
| 42. | Yuan SM, Lin HZ. Predictors of normalization of circulating interleukin-6 after cardiac myxoma resection. Braz J Cardiovasc Surg, 2019, 34(1): 22-27. |
| 43. | Ezerioha N, Feng W. Intracardiac myxoma, cerebral aneurysms and elevated interleukin-6. Case Rep Neurol, 2015, 7(2): 152-155. |
| 44. | Aguilar C, Carbajal T, Beltran BE, et al. Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin-6 and matrix metalloproteinases. Neuropathology, 2021, 41(1): 49-57. |
| 45. | Wu XL, Yang DY, Tan DJ, et al. Inhibitory effect of atorvastatin on the cell growth of cardiac myxomas via the PTEN and PHLPP2 phosphatase signaling pathway. Oncol Rep, 2013, 30(2): 757-762. |
| 46. | Bandettini WP, Karageorgiadis AS, Sinaii N, et al. Growth hormone and risk for cardiac tumors in Carney complex. Endocr Relat Cancer, 2016, 23(9): 739-746. |
| 47. | Sakamoto H, Sakamaki T, Kanda T, et al. Vascular endothelial growth factor is an autocrine growth factor for cardiac myxoma cells. Circ J, 2004, 68(5): 488-493. |
| 48. | Chen J, Wang J, Sun H, et al. Fetal cardiac tumor: Echocardiography, clinical outcome and genetic analysis in 53 cases. Ultrasound Obstet Gynecol, 2019, 54(1): 103-109. |
| 49. | Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol, 2013, 49(4): 243-254. |
| 50. | Caban C, Khan N, Hasbani DM, et al. Genetics of tuberous sclerosis complex: Implications for clinical practice. Appl Clin Genet, 2017, 10: 1-8. |
| 51. | Mariscal-Mendizábal LF, Sevilla-Montoya R, Martínez-García AJ, et al. Clinical and genetic description of patients with prenatally identified cardiac tumors. Prenat Diagn, 2019, 39(11): 998-1004. |
| 52. | Yuan SM. Interleukin-6 and cardiac operations. Eur Cytokine Netw, 2018, 29(1): 1-15. |
| 53. | Tyebally S, Chen D, Bhattacharyya S, et al. Cardiac tumors: JACC CardioOncology state-of-the-art review. JACC CardioOncol, 2020, 2(2): 293-311. |
| 54. | Barravecchia I, Mariotti S, Pucci A, et al. MICAL2 is expressed in cancer associated neo-angiogenic capillary endothelia and it is required for endothelial cell viability, motility and VEGF response. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(9): 2111-2124. |
| 55. | Sugalska M, Tomik A, Jóźwiak S, et al. Treatment of cardiac rhabdomyomas with mTOR inhibitors in children with tuberous sclerosis complex—A systematic review. Int J Environ Res Public Health, 2021, 18(9): 4907. |
| 56. | Barnes BT, Procaccini D, Crino J, et al. Maternal sirolimus therapy for fetal cardiac rhabdomyomas. N Engl J Med, 2018, 378(19): 1844-1845. |
| 57. | Prentzell MT, Rehbein U, Cadena Sandoval M, et al. G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell, 2021, 184(3): 655-674.e27. |
| 58. | Rehbein U, Prentzell MT, Cadena Sandoval M, et al. The TSC complex-mTORC1 axis: From lysosomes to stress granules and back. Front Cell Dev Biol, 2021, 9: 751892. |
- 1. Burke A, Tavora F. The 2015 WHO classification of tumors of the heart and pericardium. J Thorac Oncol, 2016, 11(4): 441-452.
- 2. Poterucha TJ, Kochav J, O'Connor DS, et al. Cardiac tumors: Clinical presentation, diagnosis, and management. Curr Treat Options Oncol, 2019, 20(8): 66.
- 3. Maleszewski JJ, Anavekar NS, Moynihan TJ, et al. Pathology, imaging, and treatment of cardiac tumours. Nat Rev Cardiol, 2017, 14(9): 536-549.
- 4. Bussani R, Castrichini M, Restivo L, et al. Cardiac tumors: Diagnosis, prognosis, and treatment. Curr Cardiol Rep, 2020, 22(12): 169.
- 5. Garatti A, Nano G, Canziani A, et al. Surgical excision of cardiac myxomas: Twenty years experience at a single institution. Ann Thorac Surg, 2012, 93(3): 825-831.
- 6. Paraskevaidis IA, Michalakeas CA, Papadopoulos CH, et al. Cardiac tumors. ISRN Oncol, 2011, 2011: 208929.
- 7. Jain D, Maleszewski JJ, Halushka MK. Benign cardiac tumors and tumorlike conditions. Ann Diagn Pathol, 2010, 14(3): 215-230.
- 8. Velez Torres JM, Martinez Duarte E, Diaz-Perez JA, et al. Cardiac myxoma: Review and update of contemporary immunohistochemical markers and molecular pathology. Adv Anat Pathol, 2020, 27(6): 380-384.
- 9. Samanidis G, Khoury M, Balanika M, et al. Current challenges in the diagnosis and treatment of cardiac myxoma. Kardiol Pol, 2020, 78(4): 269-277.
- 10. Campisi A, Ciarrocchi AP, Asadi N, et al. Primary and secondary cardiac tumors: Clinical presentation, diagnosis, surgical treatment, and results. Gen Thorac Cardiovasc Surg, 2022, 70(2): 107-115.
- 11. Paraf F. Pathology of primary cardiac tumors. Ann Pathol, 2021, 41(1): 50-57.
- 12. Teng F, Yang S, Chen D, et al. Cardiac fibroma: A clinicopathologic study of a series of 12 cases. Cardiovasc Pathol, 2022, 56: 107381.
- 13. Cresti A, Chiavarelli M, Glauber M, et al. Incidence rate of primary cardiac tumors: A 14-year population study. J Cardiovasc Med (Hagerstown), 2016, 17(1): 37-43.
- 14. Neuville A, Collin F, Bruneval P, et al. Intimal sarcoma is the most frequent primary cardiac sarcoma: Clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas. Am J Surg Pathol, 2014, 38(4): 461-469.
- 15. Joshi M, Kumar S, Noshirwani A, et al. The current management of cardiac tumours: A comprehensive literature review. Braz J Cardiovasc Surg, 2020, 35(5): 770-780.
- 16. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: Diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab, 2001, 86(9): 4041-4046.
- 17. Groussin L, Horvath A, Jullian E, et al. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab, 2006, 91(5): 1943-1949.
- 18. Forlino A, Vetro A, Garavelli L, et al. PRKACB and Carney complex. N Engl J Med, 2014, 370(11): 1065-1067.
- 19. Bouys L, Bertherat J. Management of endocrine disease: Carney complex: Clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene. Eur J Endocrinol, 2021, 184(3): R99-R109.
- 20. Tseng IC, Huang WJ, Jhuang YL, et al. Microinsertions in PRKACA cause activation of the protein kinase A pathway in cardiac myxoma. J Pathol, 2017, 242(2): 134-139.
- 21. Hinton RB, Prakash A, Romp RL, et al. Cardiovascular manifestations of tuberous sclerosis complex and summary of the revised diagnostic criteria and surveillance and management recommendations from the International Tuberous Sclerosis Consensus Group. J Am Heart Assoc, 2014, 3(6): e001493.
- 22. Peron A, Au KS, Northrup H. Genetics, genomics, and genotype-phenotype correlations of TSC: Insights for clinical practice. Am J Med Genet C Semin Med Genet, 2018, 178(3): 281-290.
- 23. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 1997, 277(5327): 805-808.
- 24. European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell, 1993, 75(7): 1305-1315.
- 25. Dibble CC, Elis W, Menon S, et al. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell, 2012, 47(4): 535-546.
- 26. Salussolia CL, Klonowska K, Kwiatkowski DJ, et al. Genetic etiologies, diagnosis, and treatment of tuberous sclerosis complex. Annu Rev Genomics Hum Genet, 2019, 20: 217-240.
- 27. Dragoumi P, O'Callaghan F, Zafeiriou DI. Diagnosis of tuberous sclerosis complex in the fetus. Eur J Paediatr Neurol, 2018, 22(6): 1027-1034.
- 28. Lee E, Mahani MG, Lu JC, et al. Primary cardiac tumors associated with genetic syndromes: A comprehensive review. Pediatr Radiol, 2018, 48(2): 156-164.
- 29. Onodera S, Nakamura Y, Azuma T. Gorlin syndrome: Recent advances in genetic testing and molecular and cellular biological research. Int J Mol Sci, 2020, 21(20): 7559.
- 30. Fu X, Niu W, Li J, et al. Activating mutation of PDGFRB gene in a rare cardiac undifferentiated intimal sarcoma of the left atrium: A case report. Oncotarget, 2017, 8(46): 81709-81716.
- 31. Ito Y, Maeda D, Yoshida M, et al. Cardiac intimal sarcoma with PDGFRβ mutation and co-amplification of PDGFRα and MDM2: An autopsy case analyzed by whole-exome sequencing. Virchows Arch, 2017, 471(3): 423-428.
- 32. Salvador-Coloma C, Saigí M, Díaz-Beveridge R, et al. Identification of actionable genetic targets in primary cardiac sarcomas. Onco Targets Ther, 2019, 12: 9265-9275.
- 33. Leduc C, Jenkins SM, Sukov WR, et al. Cardiac angiosarcoma: Histopathologic, immunohistochemical, and cytogenetic analysis of 10 cases. Hum Pathol, 2017, 60: 199-207.
- 34. Yan L, Li J, Wu Q, et al. Specific miRNA expression profile in the blood serum of cardiac myxoma patients. Oncol Lett, 2018, 16(4): 4235-4242.
- 35. Zhang J, Wang C, Xu H. miR-217 suppresses proliferation and promotes apoptosis in cardiac myxoma by targeting interleukin-6. Biochem Biophys Res Commun, 2017, 490(3): 713-718.
- 36. Cao Q, Dong P, Wang Y, et al. miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D. Oncol Rep, 2015, 33(5): 2606-2612.
- 37. Qiu Y, Yang J, Bian S, et al. PPARγ suppresses the proliferation of cardiac myxoma cells through downregulation of MEF2D in a miR-122-dependent manner. Biochem Biophys Res Commun, 2016, 474(3): 560-565.
- 38. Cheng N, Wu Y, Zhang H, et al. Identify the critical protein-coding genes and long noncoding RNAs in cardiac myxoma. J Cell Biochem, 2019, 120(8): 13441-13452.
- 39. Shiohama T, Fujii K, Miyashita T, et al. MicroRNAs profiling in fibroblasts derived from patients with Gorlin syndrome. J Hum Genet, 2019, 64(8): 757-765.
- 40. Pucci A, Mattioli C, Matteucci M, et al. Cell differentiation in cardiac myxomas: Confocal microscopy and gene expression analysis after laser capture microdissection. Heart Vessels, 2018, 33(11): 1403-1410.
- 41. Scalise M, Torella M, Marino F, et al. Atrial myxomas arise from multipotent cardiac stem cells. Eur Heart J, 2020, 41(45): 4332-4345.
- 42. Yuan SM, Lin HZ. Predictors of normalization of circulating interleukin-6 after cardiac myxoma resection. Braz J Cardiovasc Surg, 2019, 34(1): 22-27.
- 43. Ezerioha N, Feng W. Intracardiac myxoma, cerebral aneurysms and elevated interleukin-6. Case Rep Neurol, 2015, 7(2): 152-155.
- 44. Aguilar C, Carbajal T, Beltran BE, et al. Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin-6 and matrix metalloproteinases. Neuropathology, 2021, 41(1): 49-57.
- 45. Wu XL, Yang DY, Tan DJ, et al. Inhibitory effect of atorvastatin on the cell growth of cardiac myxomas via the PTEN and PHLPP2 phosphatase signaling pathway. Oncol Rep, 2013, 30(2): 757-762.
- 46. Bandettini WP, Karageorgiadis AS, Sinaii N, et al. Growth hormone and risk for cardiac tumors in Carney complex. Endocr Relat Cancer, 2016, 23(9): 739-746.
- 47. Sakamoto H, Sakamaki T, Kanda T, et al. Vascular endothelial growth factor is an autocrine growth factor for cardiac myxoma cells. Circ J, 2004, 68(5): 488-493.
- 48. Chen J, Wang J, Sun H, et al. Fetal cardiac tumor: Echocardiography, clinical outcome and genetic analysis in 53 cases. Ultrasound Obstet Gynecol, 2019, 54(1): 103-109.
- 49. Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol, 2013, 49(4): 243-254.
- 50. Caban C, Khan N, Hasbani DM, et al. Genetics of tuberous sclerosis complex: Implications for clinical practice. Appl Clin Genet, 2017, 10: 1-8.
- 51. Mariscal-Mendizábal LF, Sevilla-Montoya R, Martínez-García AJ, et al. Clinical and genetic description of patients with prenatally identified cardiac tumors. Prenat Diagn, 2019, 39(11): 998-1004.
- 52. Yuan SM. Interleukin-6 and cardiac operations. Eur Cytokine Netw, 2018, 29(1): 1-15.
- 53. Tyebally S, Chen D, Bhattacharyya S, et al. Cardiac tumors: JACC CardioOncology state-of-the-art review. JACC CardioOncol, 2020, 2(2): 293-311.
- 54. Barravecchia I, Mariotti S, Pucci A, et al. MICAL2 is expressed in cancer associated neo-angiogenic capillary endothelia and it is required for endothelial cell viability, motility and VEGF response. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(9): 2111-2124.
- 55. Sugalska M, Tomik A, Jóźwiak S, et al. Treatment of cardiac rhabdomyomas with mTOR inhibitors in children with tuberous sclerosis complex—A systematic review. Int J Environ Res Public Health, 2021, 18(9): 4907.
- 56. Barnes BT, Procaccini D, Crino J, et al. Maternal sirolimus therapy for fetal cardiac rhabdomyomas. N Engl J Med, 2018, 378(19): 1844-1845.
- 57. Prentzell MT, Rehbein U, Cadena Sandoval M, et al. G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell, 2021, 184(3): 655-674.e27.
- 58. Rehbein U, Prentzell MT, Cadena Sandoval M, et al. The TSC complex-mTORC1 axis: From lysosomes to stress granules and back. Front Cell Dev Biol, 2021, 9: 751892.