Molecular genetic analyses of central nervous system germ cell tumors in children aged ≤5 years old

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16909
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Saitama Children's Medical Center
• Principal Investigator: Fukuoka Kohei 埼玉県立小児医療センター (臨床研究部), 血液腫瘍科, 医長 (60746717)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 中枢神経胚細胞腫瘍 / 乳幼児期発症 / 分子遺伝学的解析

Outline of Final Research Achievements

Of these 16 cases, four were pathological yolk sac tumors and 12 were noted to be teratomas, in contrast to high prevalence of germinoma in older children and adult.2 cases out of 8 recurrent cases relapsed as different types of GCT, so-called “metachronous GCT”, more than 5 years after onset.
Molecular genetic analyses revealed SMARCA4, TP53, and PTEN mutations in one of the teratoma cases. DNA methylation analysis revealed that infantile teratoma and yolk sac tumor were clustered together in older children, except for the SMARCA4 mutant teratoma, which was classified as an atypical teratoid/rhabdoid tumor harboring SMARCA4 mutation.Copy number analysis presented 12p gain, which is regarded as a poor prognostic factor in older aged GCT, in four cases, consisting of three yolk sac tumors and one relapsed teratoma case.Overall, a subset of infantile CNS-GCT may be clinically and molecularly different from its tumor counterpart observed in older children and adults.

Free Research Field

小児科科学

Academic Significance and Societal Importance of the Research Achievements

頭蓋内胚細胞腫は、海外では非常に稀な上、診断、治療方針の相違のため、海外では中枢神経胚細胞腫の診断時に腫瘍生検を行わない事が多いため、検体そのものが存在しない事が多く、低年齢発症の頭蓋内胚細胞腫に関する研究は、臨床、分子遺伝学的解析ともに、日本でも未だ行われておらず、本研究は、国内、国外初の研究となる。本研究により、乳幼児発症中枢神経胚細胞腫瘍の多様性が明らかになり、今後の更なる病態解明につながる可能性がある。