Cancer esearch apeutics , Targets , and Chemical Biology e of LIM and SH 3 Protein 1 ( LASP 1 ) in the Metastatic R emination of Medulloblastoma

Downlo ulloblastoma is the most common malignant pediatric brain tumor and is one of the leading causes of -related mortality in children. Treatment failure mainly occurs in children harboring metastatic tumors, typically carry an isochromosome 17 or gain of 17q, a common hallmark of intermediate and high-risk loblastoma. Through mRNA expression profiling, we identified LIM and SH3 protein 1 (LASP1) as one of st upregulated genes on chromosome 17q in tumors with 17q gain. In an independent validation cohort medulloblastoma samples, the abundance of LASP1 mRNA was significantly associated with 17q gain, tatic dissemination, and unfavorable outcome. LASP1 protein expression was analyzed by immunohemistry in a large cohort of patients (n = 207), and high protein expression levels were found to be ly correlated with 17q gain, metastatic dissemination, and inferior overall and progression-free survival. o experiments in medulloblastoma cell lines showed a strong reduction of cell migration, increased on, and decreased proliferation upon LASP1 knockdown by small interfering RNA–mediated silencing, adhesi further indicating a functional role for LASP1 in the progression and metastatic dissemination of medulloblastoma. Cancer Res; 70(20); 8003–14. ©2010 AACR.