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Synonymous mutation in TP53 results in a cryptic splice site affecting its DNA-binding site in an adolescent with two primary sarcomas.

ABSTRACT: Pathologic variants in TP53 are known risk factors for the development of cancer. We report a 17-year-old male who presented with two primary sarcomas. Germline sequencing revealed a novel TP53 c.672 G>A mutation. Sequencing revealed wild-type TP53 in the parents, and there was no history of cancer in first-degree relatives. This de novo synonymous germline mutation results in a 5' cryptic splice site that is bound by U1, resulting in a shift of the splice site by 5 base pairs. The frame shift results in a truncated protein at residue 246, which disrupts the DNA-binding domain of p53.

SUBMITTER: Austin F

PROVIDER: S-EPMC5937697 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Synonymous mutation in TP53 results in a cryptic splice site affecting its DNA-binding site in an adolescent with two primary sarcomas.

Austin Frances F Oyarbide Usua U Massey Gita G Grimes Margaret M Corey Seth J SJ

Pediatric blood & cancer 20170505 11

Pathologic variants in TP53 are known risk factors for the development of cancer. We report a 17-year-old male who presented with two primary sarcomas. Germline sequencing revealed a novel TP53 c.672 G>A mutation. Sequencing revealed wild-type TP53 in the parents, and there was no history of cancer in first-degree relatives. This de novo synonymous germline mutation results in a 5' cryptic splice site that is bound by U1, resulting in a shift of the splice site by 5 base pairs. The frame shift r ...[more]

PMID: 28475293

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