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    GENE:

    TSC1 (TSC complex subunit 1)

    i
    Other names: TSC1, TSC Complex Subunit 1, Tuberous Sclerosis 1 Protein, TSC, Tuberous Sclerosis 1, Truncated Hemartin, KIAA0243, LAM
    10d
    Utility of Next-Generation Sequencing in Renal Neoplasia, Including Tumors With Clear Cytoplasm and Rare Phenotypes (ELOC/MITF Alterations and Mismatch Repair Deficiency). (PubMed, Mayo Clin Proc)
    Next-generation sequencing-based molecular profiling had clinical utility in two-thirds of patients, and the greatest benefit was within the broad category of ccRCN. Our results suggest that GPNMB expression was helpful in separating ELOC-RCCfms from M/TSC-RCCfms. Other benefits of NGS include subtyping high-grade RCC/RCC type not otherwise specified and identification of rare phenotypes.
    Journal • Next-generation sequencing • Mismatch repair
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    mTOR (Mechanistic target of rapamycin kinase) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • CA9 (Carbonic anhydrase 9) • GPNMB (Glycoprotein Nmb) • MITF (Melanocyte Inducing Transcription Factor)
    16d
    PAX8-positive conventional urothelial carcinomas of the urinary bladder and their distinct molecular profiles - A clinicopathologic study of 101 consecutive cases with next-generation sequencing in 20 cases. (PubMed, Histopathology)
    A subset of conventional UCs of the urinary bladder without subtype morphology and/or divergent differentiation are PAX8-positive and have frequent alterations in TERT promoter, TSC1, NOTCH1, and WT1, with an absence of RB1 loss. PAX8 positivity should be interpreted with caution if UC is in the differential, and NGS could be helpful in diagnostic workups as this study shows PAX8-positive UCs may have a distinct molecular profile.
    Journal • Next-generation sequencing
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    RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • WT1 (WT1 Transcription Factor) • TSC1 (TSC complex subunit 1) • PAX8 (Paired box 8)
    17d
    Clinicopathological and molecular features of acquired cystic disease-associated renal cell carcinoma (PubMed, Zhonghua Bing Li Xue Za Zhi)
    ACD-RCC is a rare renal cell carcinoma that occurs in patients with end-stage renal disease and has unique morphological features. It is often associated with favorable prognosis and alterations in genes related to the MTOR/TSC pathway or chromatin modification.
    Journal
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    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • KMT2C (Lysine Methyltransferase 2C) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • MME (Membrane Metalloendopeptidase) • KMT2B (Lysine Methyltransferase 2B) • GATA3 (GATA binding protein 3) • PAX8 (Paired box 8) • TFEB (Transcription Factor EB 2)
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    TP53 mutation
    27d
    Malignant progression of SEGA-imitating fibrous meningioma in a child carrying a germline CHEK2 mutation. (PubMed, Pathobiology)
    Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.
    Journal
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    TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • TSC1 (TSC complex subunit 1)
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    CHEK2 mutation
    27d
    A rare early-onset bilateral renal cysts, focal seizures in a 1-year-old male with tuberous sclerosis and No mutation identified. (PubMed, Oxf Med Case Reports)
    This case highlights the importance of considering TSC as a potential diagnosis in cases of early-onset renal cystic disease, even in the absence of detectable TSC gene mutations. Additionally, the case emphasizes the risk of severe renal involvement in TSC, necessitating early recognition and management.
    Journal
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    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
    27d
    A Phase I Trial of Combination Gemcitabine and Nab-Sirolimus in Advanced Leiomyosarcomas or Advanced Soft-Tissue Sarcomas With TSC2 or TSC1 Loss-of-function Mutations or Deletions (clinicaltrials.gov)
    P1, N=18, Active, not recruiting, M.D. Anderson Cancer Center | N=12 --> 18
    Enrollment change
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    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1)
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    gemcitabine • Fyarro (nanoparticle albumin-bound rapamycin)
    1m
    Alternative Lengthening of Telomeres in Malignant PEComas: Correlation with Molecular Features Including ATRX Gene Mutation Status. (PubMed, Mod Pathol)
    Our study provides the first correlation between ALT and genomic features of malignant PEComas, demonstrating that ATRX alterations invariably predict ALT, but that a subset of tumors without mutations in known ALT suppressor genes also activate ALT. These findings confirm that the association between ATRX alterations and ALT observed in other tumor types applies to PEComas and indicate that in a subset of cases, ALT may be activated by ATRX independent mechanisms.
    Journal
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    ATRX (ATRX Chromatin Remodeler) • TSC1 (TSC complex subunit 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3)
    1m
    Identification of Predictive Genomic Biomarkers in Metastatic Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis of Real-World Clinicogenomic Data. (PubMed, JCO Precis Oncol)
    These findings require prospective validation to confirm their clinical utility.
    Journal • Real-world evidence • IO biomarker
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    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)
    1m
    Renal Angiomyolipoma in a Young Woman With Tuberous Sclerosis: A Case Report. (PubMed, Clin Case Rep)
    This case underscores the importance of nephrectomy for managing large angiomyolipomas to alleviate symptoms and improve quality of life. Managing such patients requires a multidisciplinary approach, including imaging and genetic testing, with ongoing care and surveillance to achieve better outcomes.
    Journal
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    TSC1 (TSC complex subunit 1)
    1m
    Primary and secondary pseudo-stability and progression after atezolizumab with and without bevacizumab. (PubMed, J Immunother Cancer)
    Primary and secondary pseudo-stability/progression occur in a non-trivial proportion of patients across cancer types. Outcomes after pseudo-stability/progression are dependent on cancer type and initial response. Uncovering the clinical and molecular features of pseudo-stability/progression subtypes may guide treatment decisions and identify patients who may benefit from continued immunotherapy despite radiographic progression.
    Journal
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    TSC1 (TSC complex subunit 1)
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    Avastin (bevacizumab) • Tecentriq (atezolizumab)
    1m
    Recent advances in understanding the pathogenesis, diagnosis, and treatment of tuberous sclerosis complex (TSC)-associated Lymphangioleiomyomatosis. (PubMed, Biochem Pharmacol)
    mTOR inhibitors, such as sirolimus, remain the cornerstone therapy, but variable treatment responses highlight the need for personalized approaches. Nevertheless, more studies are needed to better understand LAM, develop more powerful diagnostic, prognostic, and predictive biomarkers, and optimize the current treatments of LAM while developing novel therapeutic approaches.
    Review • Journal
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    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • SPHK1 (Sphingosine Kinase 1)
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    sirolimus
    1m
    Chromophobe thyroid carcinoma: a distinct entity associated with TSC gene alterations. (PubMed, Virchows Arch)
    None harbored common mutations like BRAF p.V600E and RAS. CTC is a distinct, rare thyroid carcinoma often linked to TSC or TSC mutations, characterized by unique morphology and immunophenotype.
    Journal
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    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • TSC2 (TSC complex subunit 2) • RAS (Rat Sarcoma Virus) • TSC1 (TSC complex subunit 1) • NKX2-1 (NK2 Homeobox 1) • PAX8 (Paired box 8)
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    BRAF V600E • BRAF V600