ATRT-11. LIN28A promotes tumor growth and metastasis in atypical teratoid/rhabdoid tumors (AT/RT)

Atypical teratoid/rhabdoid tumors (AT/RT) are rare, malignant CNS tumors, defined by loss of SMARCB1 or rarely SMARCA4. The stem cell factor LIN28A is involved in the maintenance of pluripotency in embryonic stem cells. LIN28A expression has been reported in AT/RT, yet its tumor-specific functions and clinical implications remain mostly unknown. In this study, we analyzed the expression of LIN28A in a case series of 101 AT/RT with relation to clinicopathological and molecular features. To further explore the functional impact of LIN28A expression in AT/RT, the stem cell factor was overexpressed in AT/RT cell lines and transgenic mouse models. Strong LIN28A expression associated with the AT/RT MYC-subtype, with M+ status of the patients and represented an independent marker of inferior prognosis. Multimodal spatial analyses revealed that intratumoral LIN28A expression correlated with increased proliferative tumor cell activity. In vitro, overexpression of LIN28A caused enhanced growth of AT/RT cell lines. Moreover, multi-omics investigations and functional experiments showcased that LIN28A impaired tumor cell adhesion to extracellular substrates. We demonstrate that LIN28A expression promotes tumor growth and dissemination in AT/RT and associates with a poor prognosis. Our study offers the rationale to consider LIN28A as a prognostic marker in AT/RTs and paves the way for future diagnostic and therapeutic implications.