RT Journal Article SR Electronic T1 Differences in RNA and microRNA Expression Between PTCH1- and SUFU-mutated Medulloblastoma JF Cancer Genomics - Proteomics JO Cancer Genomics Proteomics FD International Institute of Anticancer Research SP 335 OP 347 DO 10.21873/cgp.20264 VO 18 IS 3 A1 SIVAN GERSHANOV A1 HELEN TOLEDANO A1 NOMI PERNICONE A1 SUZANA FICHMAN A1 SHALOM MICHOWIZ A1 ALBERT PINHASOV A1 NITZA GOLDENBERG-COHEN A1 TAMAR LISTOVSKY A1 MALI SALMON-DIVON YR 2021 UL http://cgp.iiarjournals.org/content/18/3/335.abstract AB Background/Aim: Germline mutations in PTCH1 or SUFU in the sonic hedgehog (SHH) pathway cause Gorlin’s syndrome with increased risk of developing SHH-subgroup medulloblastoma. Gorlin’s syndrome precludes the use of radiotherapy (a standard component of treatment) due to the development of multiple basal cell carcinomas. Also, current SHH inhibitors are ineffective against SUFU-mutated medulloblastoma, as they inhibit upstream genes. In this study, we aimed to detect differences in the expression of genes and microRNAs between SUFU- and PTCH1-mutated SHH medulloblastomas which may hint at new treatment directions. Patients and Methods: We sequenced RNA and microRNA from tumors of two patients with germline Gorlin’s syndrome – one having PTCH1 mutation and one with SUFU mutation – followed by bioinformatics analysis to detect changes in genes and miRNAs expression in these two tumors. Expression changes were validated using qRT-PCR. Ingenuity pathway analysis was performed in search for targetable pathways. Results: Compared to the PTCH1 tumor, the SUFU tumor demonstrated lower expression of miR-301a-3p and miR-181c-5p, matrix metallopeptidase 11 (MMP11) and OTX2, higher expression of miR-7-5p and corresponding lower expression of its targeted gene, connexin 30 (GJB6). We propose mechanisms to explain the phenotypic differences between the two types of tumors, and understand why PTCH1 and SUFU tumors tend to relapse locally (rather than metastatically as in other medulloblastoma subgroups). Conclusion: Our results help towards finding new treatable molecular targets for these types of medulloblastomas.