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

• Published in: Journal of neuro-oncology Vol. 125; no. 1; pp. 75 - 78
• Main Authors: Dahlin, Anna M., Hollegaard, Mads V., Wibom, Carl, Andersson, Ulrika, Hougaard, David M., Deltour, Isabelle, Hjalmars, Ulf, Melin, Beatrice
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2015; Springer Nature B.V
• Subjects: Adolescent; Brain Neoplasms - genetics; Child; Child, Preschool; Cyclin D2 - genetics; Denmark; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genetic riation; Humans; Kruppel-Like Transcription Factors - genetics; Laboratory Investigation; Male; Medicine; Medicine & Public Health; Medulloblastoma; Medulloblastoma - genetics; Neurology; Nuclear Proteins - genetics; Oncology; Patched Receptors; Patched-1 Receptor; PNET; Polymorphism, Single Nucleotide - genetics; Primitive neuroectodermal tumors; Receptors, Cell Surface - genetics; Retrospective Studies; Sweden; Young Adult; Zinc Finger Protein Gli2; Denmark; Sweden; PNET; Genetic association studies; Primitive neuroectodermal tumors; Genetic variation; Medulloblastoma
• ISSN: 0167-594X; 1573-7373; 1573-7373
• DOI: 10.1007/s11060-015-1891-1

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.