Differences in RNA and microRNA Expression between PTCH1- And SUFU-mutated Medulloblastoma

Sivan Gershanov, Helen Toledano, Nomi Pernicone, Suzana Fichman, Shalom Michowiz, Albert Pinhasov, Nitza Goldenberg-Cohen, Tamar Listovsky, Mali Salmon-Divon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Pages (from-to)335-347
Number of pages13
JournalCancer Genomics and Proteomics
Issue number3
StatePublished - May 2021


  • Gorlin syndrome
  • Medulloblastoma
  • PTCH1
  • SUFU
  • Sonic Hedgehog


Dive into the research topics of 'Differences in RNA and microRNA Expression between PTCH1- And SUFU-mutated Medulloblastoma'. Together they form a unique fingerprint.

Cite this