鉴定一个新的 SETBP1 从头突变和 SETBP1 在肿瘤发生中的新发现。

Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis.

机构信息

Medical Genetic Institute of Henan Province, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.

National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, China.

出版信息

Orphanet J Rare Dis. 2023 May 7;18(1):107. doi: 10.1186/s13023-023-02705-6.

DOI:10.1186/s13023-023-02705-6

PMID:37150818

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10165755/

Abstract

BACKGROUND

In the past decade, SETBP1 has attracted a lot of interest on that the same gene with different type or level (germline or somatic) of variants could provoke different pathologic consequences such as Schinzel-Giedon syndrome, SETBP1 Haploinsufficiency Disorder (SETBP1-HD) and myeloid malignancies. Whole exome sequencing was conducted to detect the etiology of a pregnant woman with mental retardation. As a new oncogene and potential marker of myeloid malignancies, somatic SETBP1 variants in other cancers were rarely studied. We performed a pan-cancer analysis of SETBP1 gene in different cancers for the first time.

RESULTS

A novel heterozygous mutation of the SETBP1 gene (c.1724_1727del, p.D575Vfs*4) was found in the patient and the fetus and the mutation was predicted to result in a truncated protein. Reduced SETBP1 expression was associated with SETBP1-HD. The pan-cancer analysis of SETBP1 showed that SETBP1 overexpression should be given special attention in Bladder Urothelial Carcinoma (BLCA) and Stomach adenocarcinoma (STAD).

CONCLUSIONS

The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.

摘要

背景

在过去的十年中，SETBP1 引起了很多关注，因为具有不同类型或水平（胚系或体细胞）变异的相同基因可能会引起不同的病理后果，如 Schinzel-Giedon 综合征、SETBP1 单倍不足症（SETBP1-HD）和髓系恶性肿瘤。对一名智力迟钝的孕妇进行了全外显子组测序以检测病因。作为一种新的癌基因和髓系恶性肿瘤的潜在标志物，其他癌症中的体细胞 SETBP1 变异很少被研究。我们首次对不同癌症中的 SETBP1 基因进行了泛癌症分析。

结果

在患者及其胎儿中发现了 SETBP1 基因的一个新的杂合突变（c.1724_1727del，p.D575Vfs*4），该突变预计会导致截短的蛋白。SETBP1 表达减少与 SETBP1-HD 相关。对 SETBP1 的泛癌症分析表明，在膀胱癌（BLCA）和胃腺癌（STAD）中应特别注意 SETBP1 过表达。