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BIOMARKER:

TSC2 mutation

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Other names: TSC2, TSC Complex Subunit 2, Protein Phosphatase 1, Regulatory Subunit 160, Tuberous Sclerosis 2 Protein, Tuberin, TSC4, Tuberous Sclerosis 2, PPP1R160
Entrez ID:
Related biomarkers:
16h
The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions. (PubMed, Genes (Basel))
The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator of cell growth, proliferation, and survival...Advancements in genetic testing, prenatal screening, and precision medicine hold promise for changing the diagnostic and treatment paradigm for TSC and related mTORopathies. Herein, we explore the genetic and molecular mechanisms of TSC and other mTORopathies, emphasizing contemporary genetic methods in understanding and diagnosing the condition.
Review • Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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sirolimus
9d
Acquired Cystic Disease-Associated Renal Cell Carcinoma: A Systematic Review and Meta-analysis. (PubMed, Clin Genitourin Cancer)
In conclusion, the ACD-RCC subtype exhibited several distinct clinicopathological and genetic characteristics compared to others RCC subtypes. Further researchs are needed to assess the survival outcome and the genetic characteristics of this subtype.
Retrospective data • Review • Journal
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KMT2C (Lysine Methyltransferase 2C) • TSC2 (TSC complex subunit 2)
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KMT2C mutation • TSC2 mutation
10d
Recurrent Tuberous Sclerosis Complex​​​​​/Mammalian Target of Rapamycin Mutations Define Primary Renal Hemangioblastoma as a Unique Entity Distinct From Its Central Nervous System Counterpart. (PubMed, Am J Surg Pathol)
This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification.
Journal
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mTOR (Mechanistic target of rapamycin kinase) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • GPNMB (Glycoprotein Nmb)
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TSC1 mutation • TSC2 mutation • MTOR mutation
15d
Nutritional status as a predictive factor for paediatric tuberous sclerosis complex-associated kidney angiomyolipomas: a retrospective analysis. (PubMed, Eur J Pediatr)
While gender and genotype are known predictors, this study includes the novel finding of nutritional status as a predictor of TSC-associated kidney disease. This study sheds light on a possible complex interplay of hormonal influences, obesity, and kidney angiomyolipomas growth, and further investigations focusing on the impact of nutritional status on TSC-associated kidney disease are warranted.
Retrospective data • Journal
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TSC2 (TSC complex subunit 2)
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TSC2 mutation
23d
Deciphering the genomic landscape of Chilean cancer: Unveiling driver pathway divergence, and novel germline and actionable somatic variants (AACR 2024)
Overall, tumors have mutations mainly in TP53 (42.4%), PIK3CA (12.5%), KRAS (9.6%), PTEN (4.7%), BRCA1/2 (9%). Driver mutations were present in TP53 (42%), PIK3CA (16%), KRAS (10%), ERBB2 (7%), PTEN (7%), BRCA1/2 (8%), ATM (7%), among others. Accionable mutations were found primarily in PIK3CA (17%), KRAS (10%), ERBB2 (9%), and NTRK1/2/3 (4.8%).
BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NOTCH1 (Notch 1) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • TSC2 (TSC complex subunit 2)
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TP53 mutation • KRAS mutation • PIK3CA mutation • PTEN mutation • TSC2 mutation
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MSK-IMPACT
1m
Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma. (PubMed, Head Neck)
We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.
Journal • Next-generation sequencing • BRCA Biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • LRP1B (LDL Receptor Related Protein 1B) • TSC2 (TSC complex subunit 2) • KMT2B (Lysine Methyltransferase 2B)
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TP53 mutation • KRAS mutation • ATM mutation • TSC2 mutation
2ms
Epithelioid angiomyolipoma of the liver in a patient with Li-Fraumeni syndrome: a case report. (PubMed, Diagn Pathol)
There have been very few case reports regarding the presence of PEComa in LFS, and to the best of our knowledge, this is the first report of EAML of the liver in a patient with LFS.
Journal
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TP53 (Tumor protein P53) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TP53 mutation • TSC1 mutation • TSC2 mutation
2ms
An in-silico analysis reveals further evidence of an aggressive subset of lung carcinoids sharing molecular features of high-grade neuroendocrine neoplasms. (PubMed, Exp Mol Pathol)
Similar results were also found in two other independent validation sets comprising 101 lung NENs (24 carcinoids, 21 SCLC and 56 LCNEC) and 30 carcinoids, respectively. We herein confirmed an unexpected sharing of molecular traits along the spectrum of lung NENs, with a subset of genomically distinct aggressive carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.
Journal
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TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TSC2 (TSC complex subunit 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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TP53 mutation • MYC expression • TSC2 mutation
2ms
Neuropsychiatric manifestations of tuberous sclerosis in a young man in a psychiatric hospital in Botswana: a case report. (PubMed, J Int Med Res)
Given that psychiatry may be the first medical contact for TSC patients, especially in low-resource settings, clinicians need to be knowledgeable of various neuropsychiatric conditions and be aware of the possibility of TSC in patients that present with neurocutaneous manifestations. A multidisciplinary team approach is vital for the investigation and management of such cases.
Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
2ms
A newborn with convulsions 12 days after birth was misdiagnosed as neonatal intracranial hemorrhage: Case report. (PubMed, Medicine (Baltimore))
The TSC of neonatal tuberous sclerosis is different from that of older children. It is usually characterized by respiratory distress and arrhythmia, and may be accompanied by convulsions, but the activity between attacks is normal. However, neonatal intracranial hemorrhage can be caused by premature delivery, birth injury, hypoxia, etc. Its characteristics are acute onset, severe illness, and rapid progression. Consequently, the diagnosis of these 2 diseases should not only be based on medical imaging, but also be combined with their clinical characteristics. When the imaging features are inconsistent with the clinical diagnosis, a comprehensive evaluation should be made again. The timing and pattern of onset of neonatal convulsions can help in differential diagnosis. If there is cardiac rhabdomyoma, subependymal or cortical nodule, skin low melanoma, etc, the possibility of neonatal TSC should be considered, and the diagnosis should be made according to its diagnostic criteria to avoid or reduce misdiagnosis.
Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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sirolimus
2ms
TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex. (PubMed, Nat Commun)
In mice, Rapamycin treatment normalizes lysosomal gene expression, similar to TFEB knockout, suggesting that Rapamycin's benefit in TSC is TFEB-dependent. These results change the view of the mechanisms of mTORC1 hyperactivation in TSC and may lead to therapeutic avenues.
Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • TFEB (Transcription Factor EB 2) • RHEB (Ras Homolog, MTORC1 Binding)
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TSC1 mutation • TSC2 mutation
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sirolimus
3ms
The Evolving Landscape of Therapeutics for Epilepsy in Tuberous Sclerosis Complex. (PubMed, Biomedicines)
The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.
Review • Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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everolimus
3ms
Hyperactive mTORC1 in lung mesenchyme induces endothelial cell dysfunction and pulmonary vascular remodeling. (PubMed, J Clin Invest)
Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease caused by tuberous sclerosis complex 1/2 (TSC1/2) gene mutations in pulmonary mesenchymal cells resulting in activation of the mechanistic target of rapamycin complex 1 (mTORC1)...The proposed pathophysiologic mesenchymal ligand/ EC receptor crosstalk highlights the importance of an altered mesenchymal-EC axis in LAM and other hyperactive mTORC1-driven diseases. Since ECs in LAM patients and in Tbx4LME-CreTsc2fl/fl mice do not harbor TSC2 mutations, our study demonstrates that constitutively active mTORC1 lung mesenchymal cells orchestrate dysfunctional EC responses which contribute to pulmonary vascular remodeling.
Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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sirolimus
4ms
Malignant epithelioid angiomyolipoma (eAML)/PEComa of the kidney: A genomic landscape study. (ASCO-GU 2024)
Renal malignant eAML, also known as malignant PEComa of the kidney, is an exceedingly rare malignant tumor. Our CGP identified that the majority of cases exhibit non-germline TSC2 mutations. Interestingly, other germline alterations were found in 4/34 cases which are of unknown significance.
PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • CD36 (thrombospondin receptor) • MUTYH (MutY homolog) • FLCN (Folliculin) • MLANA (Melan-A) • FANCC (FA Complementation Group C)
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PD-L1 expression • MSI-H/dMMR • TSC2 mutation • PD-L1-L
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PD-L1 IHC 22C3 pharmDx
4ms
Analysis of inactivating TSC1 and TSC2 alterations in advanced genitourinary (GU) cancers from a real-world patient population in the Foundation Medicine genomic database. (ASCO-GU 2024)
Inactivating TSC1 and/or TSC2 alterations commonly occurred in GU cancers. A proportion of GU tumors have a low TMB and/or are microsatellite stable, suggesting that TSC1 and TSC2 inactivating alterations may be driver mutations rather than passenger mutations in those tumors. Therefore, patients with inactivating alterations in TSC1 or TSC2 may benefit from mTOR inhibition via nab-sirolimus.
Clinical • Real-world evidence • Tumor mutational burden • Genomic data • Real-world • Metastases
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TP53 mutation • TMB-L • TSC1 mutation • TSC2 mutation
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Fyarro (nanoparticle albumin-bound rapamycin)
4ms
Clinical outcomes of fetuses with cardiac rhabdomyoma: A case series from a tertiary center. (PubMed, J Obstet Gynaecol Res)
Cardiac rhabdomyoma is a rare fetal and pediatric pathology that generally is a remarkable finding in the clinical process of TSC. Therefore, cases should be evaluated multisystemically and genetic counseling should be given to the family.
Clinical data • Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
4ms
Real-world analysis of patients with advanced gastrointestinal (GI) cancers harboring inactivating TSC1 and TSC2 alterations using the Foundation Medicine genomic database. (ASCO-GI 2024)
In exploratory biomarker analyses of patients with perivascular epithelioid cell tumors treated with the mTOR inhibitor nab-sirolimus (AMPECT, NCT02494570), those with inactivating alterations in the tumor suppressor genes TSC1 or TSC2 (critical negative regulators of mTOR activity) had confirmed responses (8/9 patients with inactivating TSC2 alterations and 1/5 patients with inactivating TSC1 alterations)...TSC1 and/or TSC2 alterations were commonly observed in GI cancers. These cancers were frequently microsatellite stable and of low TMB suggesting that these are actionable alterations that may be candidates for targeted therapy. This hypothesis is being tested in the PRECISION 1 (NCT05103358) trial which is open for enrollment or just-in-time clinical trial sites and available to patients with GI cancers harboring TSC1 or TSC2 alterations.
Clinical • Real-world evidence • Tumor mutational burden • Genomic data • Real-world • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TP53 mutation • KRAS mutation • TMB-L • TSC1 mutation • TSC2 mutation
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Fyarro (nanoparticle albumin-bound rapamycin)
4ms
Not all kidney cysts are created equal: a distinct renal cystogenic mechanism in tuberous sclerosis complex (TSC). (PubMed, Front Physiol)
TSC1 and TSC2 code for the proteins harmartin and tuberin, respectively, which form a complex that regulates the mechanistic target of rapamycin complex 1 (mTORC1) and prevents uncontrollable cell growth...These results unequivocally demonstrate the critical role that FOXI1 and A-IC cells, along with H-ATPase, play in TSC kidney cystogenesis. This review article will discuss the latest research into the causes of kidney cystogenesis in TSC with a focus on possible therapeutic options for this devastating disease.
Review • Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • PKD1 (Polycystin 1) • TERC (Telomerase RNA Component) • PRKD1 (Protein Kinase D1)
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TSC1 mutation • TSC2 mutation • PKD1 mutation
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sirolimus
4ms
Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT. (PubMed, Virchows Arch)
Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations.
Review • Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • NOTCH4 (Notch 4) • GATA3 (GATA binding protein 3) • PAX8 (Paired box 8)
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PIK3CA mutation • NF2 mutation • TSC1 mutation • TSC2 mutation • MTOR mutation • PAX8 positive
4ms
Clinical Features and Associated Factors of Epilepsy in Patients with Tuberous Sclerosis Complex: A Retrospective Observational Study (AES 2023)
Overall multidisciplinary awareness and evaluation, including genetic test and neuro-imaging, are vital for early diagnosis and adequate management of TSC. Further studies to determine the predictive factors of disease outcome are urgently needed.
Observational data • Retrospective data
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC2 mutation
4ms
An in-vitro Testing Platform to Assess Functional Effects of Distinct Tsc2 Mutations on Neuronal Morphology and mTOR Signaling (AES 2023)
The disease is caused by mutations in Tsc1 or Tsc2 genes, which lead to altered cell signal transduction, most prominently hyperactivation of the mechanistic target of rapamycin (mTOR) pathway... We have established a scalable platform to characterize Tsc2 mutations. Our model replicates key phenotypes seen in patient tissue samples and other Tsc2 mutation models, such as enlarged neuronal soma size and altered signal transduction, that can be rescued by gene replacement. In the future, this testing platform will allow us to rapidly establish genotype-phenotype relationships for patient-specific Tsc2 mutations, making a personalized medicine approach for TSC feasible.
Preclinical
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TSC2 (TSC complex subunit 2)
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TSC1 mutation • TSC2 mutation • MTOR mutation • TSC2 deletion
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sirolimus
4ms
Pathology of hereditary renal cell carcinoma syndromes: Tuberous sclerosis complex (TSC). (PubMed, Semin Diagn Pathol)
TSC is caused by inactivating mutations in TSC1/TSC2, which encodes hamartin and tuberin, respectively, and forms a complex that regulates mechanistic target of rapamycin complex 1 (mTORC1), resulting in cell overgrowth and oncogenesis. Since a leading cause of morbidity and mortality in TSC relates to chronic kidney disease and the ability to preserve renal function, this review describes the important pathologic findings in TSC-associated renal neoplasms and their correlating sporadic counterparts. The most common renal tumor in TSC patients are AMLs, followed by a heterogeneous spectrum of renal epithelial tumors, which may provide clues to establishing a diagnosis of TSC.
Review • Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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sirolimus
5ms
Next-generation sequencing of uveal melanoma with clinical and histological correlations: Prognostic value of new mutations in the PI3K/AKT/mTOR pathway. (PubMed, Clin Exp Ophthalmol)
BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.
Journal • Next-generation sequencing
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SF3B1 (Splicing Factor 3b Subunit 1) • BAP1 (BRCA1 Associated Protein 1) • TOP2A (DNA topoisomerase 2-alpha) • LRP1B (LDL Receptor Related Protein 1B) • FGFR4 (Fibroblast growth factor receptor 4) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • DHX9 (DExH-Box Helicase 9)
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SF3B1 mutation • BAP1 mutation • CHEK2 mutation • TSC2 mutation • MTOR mutation • RAD51B mutation
5ms
Genetic diffuse cystic lung disease in adults (PubMed, Rev Mal Respir)
Future challenges in these often under-recognized diseases include the need to reduce the delay to diagnosis, and to develop potentially curative treatments. In France, physicians can seek help from the network of reference centers for the diagnosis and management of rare pulmonary diseases.
Review • Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • FLCN (Folliculin)
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TSC1 mutation • TSC2 mutation • FLCN mutation
5ms
Treatment of tuberous sclerosis complex manifestations in children with mTOR inhibitors. (PubMed, Childs Nerv Syst)
The utilization of mTOR inhibition in TSC is expected to become more prevalent in clinical practice, as current research is anticipated to provide a better understanding of the therapeutic roles of these treatments in TSC.
Journal
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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everolimus
5ms
TSC2 S1365A mutation potently regulates CD8+T cell function and differentiation improving adoptive cellular cancer therapy. (PubMed, JCI Insight)
These findings reveal an upstream mechanism to regulate mTORC1 activity in T cells. The TSC2-SA mutation enhances both T cell effector function and long-term persistence/memory formation, supporting an approach to engineer better CAR-T cells for treating cancer.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • TSC2 (TSC complex subunit 2)
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CD8 expression • TSC2 mutation • MTOR mutation
5ms
Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential selection for adjuvant therapy (EMUC 2023)
 Presence of somatic “non-VHL” mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions These findings support the prognostic value of “non-VHL” mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant therapy.
Clinical
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • VHL (von Hippel-Lindau tumor suppressor) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)
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ATM mutation • PTEN mutation • PBRM1 mutation • BAP1 mutation • VHL mutation • TSC1 mutation • TSC2 mutation • MTOR mutation • SETD2 mutation
5ms
Journal
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TSC2 (TSC complex subunit 2)
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TSC2 mutation
6ms
Identifying Somatic Mosaicism for Tuberous Sclerosis Complex by Targeted Next-Generation Sequencing (KIDNEY WEEK 2023)
Patients with mild clinical features suggestive but not diagnostic of TSC can be caused by missense or mosaic TSC1/TSC2 mutations. The diagnosis of TSC SM has important implications for genetic counselling and clinical prognostication, and can be improved by NGS.
Next-generation sequencing
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
6ms
Trial primary completion date • Metastases
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TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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TSC1 mutation • TSC2 mutation
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samotolisib (LY3023414)
6ms
Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma. (PubMed, JCO Precis Oncol)
Tumor mutation profiling of cfDNA in HCC represents an alternative to tissue-based genomic profiling, given the high degree of tumor-plasma NGS concordance; however, genotyping of both blood and tumor may be required to detect all clinically actionable genomic alterations.
Journal • BRCA Biomarker • Metastases
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • TERT (Telomerase Reverse Transcriptase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • TSC2 (TSC complex subunit 2) • AFP (Alpha-fetoprotein) • TSC1 (TSC complex subunit 1)
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TP53 mutation • AFP elevation • TSC1 mutation • TSC2 mutation • TERT mutation
6ms
Osteosarcoma's genetic landscape painted by genes' mutations. (PubMed, Acta Biochim Pol)
Their role in cancerogenesis was confirmed by the analysis of available articles published previously. The results of the study indicate that examination of selected genes' mutations might help to identify patients' predisposition to OS development, as well as monitor the disease progression, and establish prognosis. However, to fully understand the pathogenesis of OS further studies are required.
Journal
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • LRP1B (LDL Receptor Related Protein 1B) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • BCOR (BCL6 Corepressor) • GNAS (GNAS Complex Locus) • NCOR1 (Nuclear Receptor Corepressor 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • PDE4DIP (Phosphodiesterase 4D Interacting Protein) • H3-3A (H3.3 Histone A) • CAMTA1 (Calmodulin Binding Transcription Activator 1) • SMAD2 (SMAD Family Member 2)
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TSC2 mutation
6ms
Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition. (PubMed, Adv Sci (Weinh))
These findings demonstrate that tissue-engineered disease modeling exposes a physiologically relevant therapeutic vulnerability that would be otherwise missed by conventional culture on plastic. This work substantiates HDAC inhibitors as possible therapeutic candidates for the treatment of patients with LAM and requires further study.
Journal
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TSC2 (TSC complex subunit 2)
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TSC2 mutation • MTOR mutation
7ms
Primary mucosal melanomas of the urogenital tract: a clinical, pathological, and genetic nationwide survey of Danish patients 1990-2019. (PubMed, Scand J Urol)
Our study highlights the rarity of urinary tract melanomas and their poor prognosis. The most widely used treatment for urogenital mucosal melanoma remains surgical while adjuvant therapy strategies are evolving. Next-generation sequencing showed mutational patterns with no location-specific patterns. The most frequent mutations were in the NF1, ATRX, NRAS, and TP53 genes.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • CREBBP (CREB binding protein) • RAC1 (Rac Family Small GTPase 1)
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TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • NF1 mutation • TSC2 mutation