Abstract Introduction Approximately 8-10% of pediatric patients with brain tumors carry cancer predisposition genes. However, the clinical presentation of cancer predisposition syndromes can be highly variable, and some patients may not show typical syndromic features, resulting in underdiagnosis. Additionally, some patients may have alterations in genes that are not yet well understood or recognized. We concentrated on variants in cancer predisposition genes that were not previously well known to be associated with brain tumors. Using a large population database, we found three variants linked to brain tumors. Methods We analyzed exome data from the UK Biobank (UKBB) database, which includes a cohort of 469, 862 individuals, including 169 cancer predisposition genes for analysis. Cancer phenotype and demographic data were collected for individuals diagnosed with brain tumors; variants were annotated with ANNOVAR. Results In the UKBB, 1, 498 patients were diagnosed with brain tumors, including 817 males and 681 females. We identified three heterozygous pathogenic/likely pathogenic variants in the genes MUTYH, MITF, and SBDS among these patients. The first variant, NM₀01048174. 2 (MUTYH): c. 1103GA (p. Gly368Asp), which is associated with colorectal cancer, was found in 21 patients. The second variant, NM₀01354604. 2 (MITF): c. 1273GA (p. Glu425Lys), known to be associated with melanoma and renal cell carcinoma, was identified in 16 patients. The last variant, NM₀16038. 4 (SBDS): c. 258 + 2TC, primarily associated with Shwachman–Diamond syndrome, was found in 14 patients. Two patients had both the MUTYH and SBDS variants, while one patient had both the MITF and SBDS variants. Conclusions The presence of these variants suggests the importance of including these genes in genetic screening for brain tumors. The co-occurrence of multiple variants in some patients could indicate a potential interaction or cumulative effect in brain tumor development. Future studies should investigate the mechanisms by which these variants contribute to brain tumors and conduct larger cohort analyses to validate these findings.
Mochizuki et al. (Fri,) studied this question.