Previously reported CCDC26 risk variant and novel germline variants in GALNT13, AR, and MYO10 associated with familial glioma in Finland

• Published in: Scientific reports Vol. 14; no. 1; p. 11562
• Main Authors: Nurminen, Riikka, Afyounian, Ebrahim, Paunu, Niina, Katainen, Riku, Isomäki, Mari, Nurminen, Anssi, Scaravilli, Mauro, Tolppanen, Jenni, Fey, Vidal, Kivinen, Anni, Helén, Pauli, Välimäki, Niko, Kesseli, Juha, Aaltonen, Lauri A., Haapasalo, Hannu, Nykter, Matti, Rautajoki, Kirsi J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/68; 631/208/69; Adult; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain tumors; Exome Sequencing; Female; Filopodia; Finland; Genetic Predisposition to Disease; Germ-Line Mutation; Glioma; Glioma - genetics; Glioma - pathology; Humanities and Social Sciences; Humans; Male; Middle Aged; multidisciplinary; N-Acetylgalactosaminyltransferases - genetics; Pedigree; Polygenic inheritance; Polypeptide N-acetylgalactosaminyltransferase; Science; Science (multidisciplinary); Finland
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-62296-5

Predisposing factors underlying familial aggregation of non-syndromic gliomas are still to be uncovered. Whole-exome sequencing was performed in four Finnish families with brain tumors to identify rare predisposing variants. A total of 417 detected exome variants and 102 previously reported glioma-related variants were further genotyped in 19 Finnish families with brain tumors using targeted sequencing. Rare damaging variants in GALNT13 , MYO10 and AR were identified. Two families carried either c.553C>T (R185C) or c.1214T>A (L405Q) on GALNT13 . Variant c.553C>T is located on the substrate-binding site of GALNT13 . AR c.2180G>T (R727L), which is located on a ligand-binding domain of AR, was detected in two families, one of which also carried a GALNT13 variant. MYO10 c.4448A>G (N1483S) was detected in two families and c.1511C>T (A504V) variant was detected in one family. Both variants are located on functional domains related to MYO10 activity in filopodia formation. In addition, affected cases in six families carried a known glioma risk variant rs55705857 in CCDC26 and low-risk glioma variants. These novel findings indicate polygenic inheritance of familial glioma in Finland and increase our understanding of the genetic contribution to familial glioma susceptibility.