Biosample Repository

As of December 1, 2024, the TSC Biosample Repository has the following in their inventory:

Whole Blood

• 265 DNA*
• 1 PBMC
• 7 DBS
• 1167 Plasma
• 1024 WBC – Buffy Coat
• 1 Whole Blood
• 1 Whole Blood (cord blood)

Buccal

• 493 Buccal Cells
• 167 DNA*
• 1 Saliva
• 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.

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

• 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.
• Rubtsova V, Chun Y, Kim J, Ramirez CB, Jung S, Choi W, Kelly ME, Lopez ML, Cassidy E, Rushing G, Aguiar DJ, Ling Lau W, Ahdoot RS, Smith M, Edinger AL, Lee S, Jang C, and Lee G. Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients. iScience, 2024 Jun. doi: 10.1016/j.isci.2024.110265. Read the article.
  • The study conducted metabolomics and utilized on plasma from kidney angiomyolipoma/cyst-positive or -negative TSC patients to identify potential diagnostic markers of kidney angiomyolipoma’s (AML) in tuberous sclerosis complex. The authors identified seven chemical markers in AML/cyst-positive samples that could point to identifying kidney/metabolic disease in TSC. These seven markers even remained significant when compared to healthy control samples.