Childhood solid tumours cancer susceptibility

Gene: ELP1

Green List (high evidence)

PMID: 32296180 (2020) - Recurrent germline LOF variants of ELP1 detected in paediatric medulloblastoma (MB) cases; specifically the Sonic Hedgehog (SHH) subgroup, in which the variants were found in 14.4% (29/202) of patients. Inheritance of germline ELP1 LOF variants was confirmed by WES of three parent-offspring trios, two of which exhibited a family history of paediatric MB. Carriers of these variants tended to develop MB(SHH) as older children (median age at diagnosis: 6.3 years). ELP1-associated MB(SHH) tumours were significantly enriched for somatic alterations of PTCH1 (Sonic Hedgehog receptor), suggesting ELP1 LOF variants predispose to tumour development in combination with constitutive activation of SHH signalling.

Created: 4 Aug 2020, 11:41 a.m. | Last Modified: 4 Aug 2020, 11:41 a.m.

Panel Version: 1.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Medulloblastoma

Publications

• 32296180

Green List (high evidence)

Medulloblastoma predisposition: association identified for heterozygous ELP1 loss of function variants with paediatric medulloblastoma with exome-wide significance, specifically associated with the sonic hedgehog (SHH) subtype. Association was validated in additional paediatric cohorts. Monoallelic germline loss of function variants identified in 29/202 paediatric medulloblastoma SHH cases (absent from adult patients) and loss of heterozygosity of the ELP1 wild-type allele was present in all tumours.
Sources: Literature

Created: 3 Jun 2020, 10:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Paediatric medulloblastoma Sonic Hedgehog subtype

Publications

• 32296180

Variants in this GENE are reported as part of current diagnostic practice