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Researchers

Biosample Repository

The TSC Biosample Repository houses human biological materials such as blood, DNA, and tissues linked to detailed clinical data in the TSC Natural History Database. High-quality biosamples and their associated clinical data will enable researchers to discover biomarkers, establish human cell lines or tissue arrays for drug testing, and search for clues to understand why TSC is so different from person to person.

Types of samples available include:

  • DNA isolated from white blood cells and buccal cells
  • White blood cell pellets
  • Plasma
  • Remnant tissue from surgeries (frozen or fixed, paraffin-embedded), including brain, kidney, and liver

The TSC Biosample Repository also provides researchers in the Americas access to the TSC1- and TSC2-knockout HEK293T cell lines from the Nellist laboratory at Erasmus MC:

  • Cell line 1C2 (TSC1-/-)
  • Cell line 3H9 (TSC2-/-)
  • Cell line 3H9-1B1 (TSC1-/-/TSC2-/-)
  • HEK 293T (parental cell line)

The Van Andel Research Institute in Grand Rapids, MI processes, stores, and delivers TSC Biosample Repository samples on behalf of the TSC Alliance. Download the HEK Cell Line Request Form. Replacement cell lines have a flat rate cost of $200 to cover shipping and staff time.

Samples Currently Available

As of September 1, 2023, the TSC Biosample Repository has the following in their inventory:

Whole Blood

  • 184 DNA*
  • 1 PBMC
  • 956 Plasma
  • 954 WBC – Buffy Coat
  • 1 Whole Blood
  • 1 Whole Blood (cord blood)

Buccal

  • 436 Buccal Cells
  • 101 DNA*
  • 1 Embedded Block (buccal mucosa)
  • 1 Glass H&E Slide (buccal mucosa)

Tissue

Please see full inventory, including tissue specimens, here.

*Please note: We are able to extract DNA from additional whole blood or buccal samples as needed.

We highly recommend you contact the TSC Alliance at biosample@tscalliance.org to discuss available samples.

Because biosamples are linked to data in the Natural History Database, applicants may request subsets of biosamples based on clinical phenotypes, age, sex, etc. Additional data from the Natural History Database relevant to the project may be requested for each sample, as well.

How to Request Samples

Please download the Application for Biosample Access and follow the instructions on pages 1-2. Prior to applying, we encourage you to discuss your project’s goals and biosample needs by emailing biosample@tscalliance.org.

All biosample requests will be reviewed by the Natural History Database and Biosample Repository Steering Committee:

Thomas Blanchard, PhD (Director, University of Maryland Brain and Tissue Bank)
Peter Crino, MD, PhD (University of Maryland Medical Center)
Petrus de Vries, PhD, MBChB, FRCPsych (University of Capetown)
Maureen Elliott (TSC Community)
Laura Farach, MD (University of Texas Health Science Center, Houston)
Nishant Gupta, MD (University of Cincinnati)
Rebecca Ihrie, PhD (Vanderbilt University)
Shafali Jeste, MD (Children’s Hospital Los Angeles)
Mark Keezer, MSc, MDCM, CSCN(EEG), PhD (Université de Montréal Hospital Centre)
Iris Mustich, MPH (TSC Community)
Elahna Paul, MD, PhD (Massachusetts General Hospital/Harvard)

Partnering Opportunities

The TSC Alliance is eager to partner with sponsors of clinical trials or clinical research studies to collect biosamples centrally at the TSC Biosample Repository. Such biosamples will remain under the control of the study’s biosample use committee until the conclusion of the project, at which time the samples will become part of the openly available TSC Biosample Repository. This provides a win-win opportunity to ensure the long-term availability of valuable samples. This process is being used with the Developmental Synaptopathies Consortium and the PREVeNT clinical trial.

Publications Using TSC Biosamples

  • Hsieh L, Wen J, Nguyen L, Zhang L, Getz S, Torres-Reveron J, Wang Y, Spencer D, and Bordey A. Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice. Sci Transl Med. 2020 Nov 18;12(570):eabc1492. doi: 10.1126/scitranslmed.abc1492.  Read the article.
    • The authors found a link between the expression of a channel protein called HCN4 (hyperpolarization-activated cyclic-gated potassium channel isoform 4) and seizure activity when present in neurons in mouse brains. They found that elevated mTOR activity led to HCN4 expression in mice and found HCN4 expression in brain tissues resected from patients with TSC.
  • Salles DC, Asrani K, Woo J, Vidotto T, Liu HB, Vidal I, Matoso A, Netto GJ, Argani P, Lotan TL. GPNMB expression identifies TSC1/2/mTOR-associated and MiT family translocation-driven renal neoplasms. J Pathol. 2022 Jun;257(2):158-171. doi: 10.1002/path.5875. Epub 2022 Mar 29. PMID: 35072947; PMCID: PMC9310781. Read the article.
    • The authors found that GPNMB (glycoprotein nonmetastatic B) was upregulated following TSC2 loss in a MiT/TFE‐ and mTORC1‐dependent fashion in cell lines. Additionally, renal tumors in Tsc2 +/− A/J mice showed upregulation of GPNMB compared with normal kidney. Mean GPNMB expression was comparable between translocation renal cell carcinomas and other TSC1/2/MTOR alteration‐associated renal tumors (including ESC, LOT, AML, and PEComa).
  • Asrani, K., Woo, J., Mendes, A.A. et al. An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss. Nat Commun 13, 6808 (2022). Read the article.
    • The authors utilized the human embryonic kidney HEK293T cells with or without somatic genomic deletion of TSC1, TSC2 or TSC1/2 via CRISPR-Cas9 genome editing from the Biosample Repository to show data indicating the existence of a negative feedback loop that constrains amino acid-induced, FLCN:FNIP2-mediated RagC activity in renal cells with constitutive mTORC1 signaling, and the resulting MiT/TFE hyperactivation may drive oncogenesis with loss of the TSC2 tumor suppressor.
  • Giannikou K, Martin KR, Abdel-Azim AG, Pamir KJ, Hougard TR, Bagwe S, Tang Y, MacKeigan JP, Kwiatkowski DJ, Henske EP, and Lam HC. Spectrum of germline and somatic mitochondrial DNA variants in Tuberous Sclerosis Complex. Front Genet. 2023 Jan 30;13:917993. doi: 10.3389/fgene.2022.917. Read the article.
    • This study aimed to assess the contributions of variation in DNA within mitochondria, a cellular structure that accumulates mutations as humans age. This is the first genetic study investigating the impact of mitochondrial genomic alterations on TSC development and disease risk. Analysis of diverse tissues from individuals with TSC revealed mitochondrial DNA alterations in 270 samples, however, these changes did not correlate with TSC clinical features, and did not differ between tumor and normal samples. The findings suggest that the mitochondrial genome does not change much across tissues and within TSC-associated tumors, and that additional research is needed to understand if these changes affect how TSC presents clinically.
  • Bhaoighill MN, Falcon-Perez JM, Royo F, Tee AR, Webber JP and Dunlop EA. Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers. J Extracell Vesicles. 2023 Jun 6;12:12336. doi: 10.1002/jev2.12336. Read the article.
    • This study is one of the first to analyze extracellular vesicles (EVs) in mTORC1-cells from plasma samples of TSC participants with TSC2. EVs act as carriers of biomolecules in the cell, including RNA and other proteins that can contribute to tumor development. The authors found that proteins linked to tumor-supporting signals causing faster cell growth were favored in EVs from TSC plasma samples compared to non-TSC samples. These findings suggest that EVs serve as an important biomarker for TSC, and that additional consideration for EV-focused mTOR treatment for TSC need to be further understood in the future.

Information for Individuals with TSC and Their Families

If you are an individual with TSC or a family member of someone with TSC, please see here for information about donating samples to the TSC Biosample Repository.

Acknowledgements

he TSC Natural History Database and Biosample Repository are governed and wholly funded by the TSC Alliance thanks to generous support from Lorne Waxlax, Bill Watts, the Cowlin Family Fund, the Engles Collaborative Research Fund, Jim and Andrea Maginn, and many additional donors through the Unlock the Cure campaign.

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