TSC1 mutation

We speculate that this new missense variant in TSC2 gene with 30% mosaicism will be associated to the milder phenotype of TS since the regression of the rhabdomyomas is the only manifestation in this patient. We hope that this case report might help clinicians and genetic counselors manage individualized surveillance plans for patients with TS.

Primary renal HB is a rare mesenchymal tumor that requires differentiation from clear cell renal cell carcinoma (CCRCC) using morphological, IHC markers, and genetic testing when necessary. TSC1 could be a specific molecular hallmark of renal HB. Additional case data is required to better understand the molecular genetic alterations of the disease.

We present a frontal lobe intra-axial parenchymal schwannoma containing a CHD7::VGLL3 gene fusion presenting in a 19 month-old male, the youngest patient yet reported for this lesion.

P2, N=18, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

This case underscores the efficacy of oral everolimus in reducing FA size in a pediatric TSC patient, with broader therapeutic benefits that support the potential of mTOR inhibition as a multi-targeted strategy for TSC management. Further studies are needed to explore the full range of applications and long-term impact of mTOR inhibitors in TSC care.

Moreover, our analysis showed that some people with TSC1/TSC2 mutations did not match diagnostic criteria. This highlights the importance of genetic testing and molecular profiling in understanding the clinical variability and aiding in the management of TSC patients.

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies.

In the second line, we corrected a missense variant in coding exon 40 within the GTPase-activating protein domain (c.5228G>A, p.R1743Q). The generation of TSC2 patient iPSCs in parallel with their corresponding CRISPR-corrected isogenic lines will be an important tool for disease modeling applications and for developing therapeutics.

Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.

All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.

P2, N=17, Active, not recruiting, National Cancer Institute (NCI) | N=209 --> 17 | Trial completion date: Jun 2024 --> Nov 2025