Skeletal dysplasia

Gene: TP53

Red List (low evidence)

This gene is rated as red, because the variants are somatic, occurring in the tumour.

Created: 29 Jan 2024, 4:42 p.m. | Last Modified: 29 Jan 2024, 4:42 p.m.

Panel Version: 4.49

PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.

Created: 22 Jan 2024, 8:29 p.m. | Last Modified: 29 Jan 2024, 4:42 p.m.

Panel Version: 4.49

Comment on mode of inheritance: TP53 variants associated with chondrosarcomas are somatic, occurring in the tumour material.

Created: 22 Jan 2024, 8:23 p.m. | Last Modified: 22 Jan 2024, 8:23 p.m.

Panel Version: 4.45

Green List (high evidence)

Inactivating mutations in TP53 are common in dedifferentiated chondrosarcoma (DDCS) and, in a subset of cases, the TP53 mutation is restricted to the dedifferentiated nonchondrogenic component (8/11, 73% of the cases tested). Half of the tumours where the conventional chondrogenic component was paired with the high-grade non-chondrogenic component showed TP53 mutation in the chondrogenic area (3/6, 50%). These findings imply that TP53 alterations occur late in tumorigenesis, potentially with a TP53-mutant subclone that progresses to the dedifferentiated component in DDCS. Identification of TP53 mutation in an otherwise low-grade central chondrosarcoma may indicate the tumor is at increased risk of dedifferentiation.
Genetic testing for TP53 along with IDH1, IDH2 and TERT promoter mutations in central conventional chondrosarcoma could be useful in patient stratification.
Sources: Literature

Created: 15 Jan 2024, 1:04 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Central conventional chondrosrcoma

Publications

• PMID: 33147331