Synonymous mutation in TP53 results in a cryptic splice site affecting its DNA‐binding site in an adolescent with two primary sarcomas. Issue 11 (5th May 2017)

• Record Type: Journal Article
• Authors: Austin, Frances; Oyarbide, Usua; Massey, Gita; Grimes, Margaret; Corey, Seth J.
• Is Part Of: Pediatric blood & cancer. Volume 64:Issue 11(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-05-05
• Subjects: Li‐Fraumeni syndrome -- sarcoma -- splicing; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.26584
• Languages: English
• ISSNs: 1545-5009

Abstract

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.