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TP53基因的同义突变导致一个隐蔽剪接位点，影响了一名患有两种原发性肉瘤的青少年患者的DNA结合位点。

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

作者信息

Austin Frances, Oyarbide Usua, Massey Gita, Grimes Margaret, Corey Seth J

机构信息

Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Children's Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia.

Department of Pathology, Virginia Commonwealth University, Richmond, Virginia.

出版信息

Pediatr Blood Cancer. 2017 Nov;64(11). doi: 10.1002/pbc.26584. Epub 2017 May 5.

DOI:10.1002/pbc.26584
PMID:28475293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5937697/
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.

摘要

TP53基因的病理变异是癌症发生的已知风险因素。我们报告了一名17岁男性，他患有两种原发性肉瘤。种系测序发现了一种新的TP53基因c.672 G>A突变。测序显示其父母的TP53基因是野生型，且一级亲属中无癌症病史。这种新发的同义种系突变导致了一个5'隐蔽剪接位点，该位点被U1结合，导致剪接位点偏移5个碱基对。移码导致在第246位残基处产生截短蛋白，这破坏了p53的DNA结合结构域。

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