Medulloblastoma

Gene: ELP1

Green List (high evidence)

PMID: 32296180
Rare germline loss-of-function variants identified in the ELP1 gene in 14% of paediatric patients with medulloblastoma in subgroup sonic hedgehog. Parent–offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the SHH-alpha subtype and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34) position. Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems.

PMID: 39184053
Germline exome sequencing in 160 childhood survivors of medulloblastoma, identified 5 LOF variants in ELP1 In 5 patients with medulloblastoma (2 x splice, 2 x nonsense, 1 frameshift).

Created: 12 Sep 2024, 10:23 p.m. | Last Modified: 12 Sep 2024, 10:23 p.m.

Panel Version: 0.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Medulloblastoma, MONDO:0007959; Medulloblastoma predisposition syndrome, MIM#155255

Publications

• PMID: 32296180, 39184053

Green List (high evidence)

Sources: Expert Review

Created: 25 Nov 2022, 9:26 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
{Medulloblastoma} 155255