CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma.

Abstract

Recent studies have described a number of genes that are frequently altered in medulloblastoma tumors and that have putative key roles in the development of the disease. We hypothesized that common germline genetic variations in these genes may be associated with medulloblastoma development. Based on recent publications, we selected 10 genes that were frequently altered in medulloblastoma: CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot samples) from 243 childhood medulloblastoma cases and 247 control subjects from Sweden and Denmark. Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P(combined) < 0.05). The findings were however not statistically significant following correction for multiple testing by the very stringent Bonferroni method. The results do not support our hypothesis that common germline genetic variants in the ten studied genes are associated with the risk of developing medulloblastoma.

• Authors: Anna M Dahlin, Mads V Hollegaard, Carl Wibom, Ulrika Andersson, David M Hougaard, Isabelle Deltour, Ulf Hjalmars, Beatrice Melin
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 125 Issue 1 Pg. 75-8 (Oct 2015) ISSN: 1573-7373 [Electronic] United States
• PMID: 26290144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCND2 protein, human
• Cyclin D2
• GLI2 protein, human
• Kruppel-Like Transcription Factors
• Nuclear Proteins
• PTCH1 protein, human
• Patched Receptors
• Patched-1 Receptor
• Receptors, Cell Surface
• Zinc Finger Protein Gli2

Topics

• Adolescent
• Brain Neoplasms (genetics)
• Child
• Child, Preschool
• Cyclin D2 (genetics)
• Denmark
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease (genetics)
• Humans
• Kruppel-Like Transcription Factors (genetics)
• Male
• Medulloblastoma (genetics)
• Nuclear Proteins (genetics)
• Patched Receptors
• Patched-1 Receptor
• Polymorphism, Single Nucleotide (genetics)
• Receptors, Cell Surface (genetics)
• Retrospective Studies
• Sweden
• Young Adult
• Zinc Finger Protein Gli2