Germ-line and somatic DICER1 mutations in pineoblastoma

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Germ-line RB-1 mutations are known to predispose to pineoblastoma (PinB).
• Other genetic factors contributing to PinB development are not well-established.
• A recent case identified a germ-line DICER1 mutation in a child with PinB.

Purpose of the Study:

• To determine the prevalence of DICER1 mutations in pineoblastoma.
• To establish DICER1 as a susceptibility gene for PinB.
• To investigate the role of DICER1 mutations in PinB pathogenesis.

Main Methods:

• Sequencing of DICER1 in blood and tumor DNA from 21 PinB cases.
• Utilized Sanger and next-generation sequencing techniques.
• Tested for somatic DICER1 mutations in one case.

Main Results:

• Identified four deleterious DICER1 mutations in 18 previously untested PinB cases.
• Three mutations were germ-line, one had undetermined origin.
• All four cases showed complete loss of DICER1 protein due to biallelic inactivation.
• No somatic DICER1 RNase IIIb mutations were found.

Conclusions:

• Germ-line DICER1 mutations significantly contribute to pineoblastoma development.
• DICER1 is confirmed as an important susceptibility gene for PinB.
• Pineoblastoma can manifest as a result of germ-line DICER1 mutations.