DICER1在儿童和成人癌症易感性人群中的患病率、表型和嵌合。

IF 6.6 1区 医学 Q1 GENETICS & HEREDITY
Lluis Salvador , Jesús del Valle , Eduard Dorca , Anne-Sophie Chong , Anne-Laure Chong , José Camacho Valenzuela , Elisabet Munté , Cristina Rioja , Laura Martí-Sánchez , Mónica Salinas , Esther Darder , Marc R. Fabian , Joan Brunet , Hector Salvador , Conxi Lázaro , Barbara Rivera
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引用次数: 0

摘要

目的:DICER1肿瘤易感综合征(DTPS)是一种影响儿童和年轻人的遗传性疾病。DICER1携带者的识别是家庭预防和行动的关键。然而,由于其不完全外显率和广泛的表型谱,DTPS的诊断受到阻碍。方法:我们对疑似癌症易感综合征的92名儿童和6108名成人的DICER1测序数据进行了分析。研究了来自选定携带者和公共数据集的临床和DICER1体细胞数据。结果:种系DICER1型pv在儿童中的患病率为1:30,在成人中的患病率为1:30 . 54。没有成人转诊表型是已知的dpps相关肿瘤,尽管3/5的携带者发生甲状腺改变。我们提供功能证据支持一种新的框架内缺失的致病性。一个56岁的妇女卵巢癌和毒性弥漫性甲状腺增生被发现有一个受精卵后热点错义。结论:DICER1 pv在癌症易感人群中的患病率是在普通人群中报道的5-6倍。儿科发病的DTPS具有很好的特征,而成人携带者主要表现为甲状腺异常,没有dicer1相关的家族史,因此当与其他肿瘤类型合并时,需要准确的识别标准。合子后热点错误可能存在,但没有预期的严重表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DICER1 in pediatric and adult cancer predisposition populations: Prevalence, phenotypes, and mosaicism

Purpose

DICER1 tumor predisposition syndrome (DTPS) is a hereditary condition affecting children and young adults. Identification of DICER1 carriers is key for prevention and actionability in families. However, DTPS diagnosis is hindered by its incomplete penetrance and broad phenotypic spectrum.

Methods

We performed an analysis of DICER1 sequencing data from 92 children and 6108 adults with suspected cancer predisposition syndrome. Clinical and DICER1 somatic data from selected carriers and public data sets were studied.

Results

The prevalence of germline DICER1 pathogenic variants was 1:30 in children and 1:3054 in adults. No adult referral phenotype was a known DTPS-associated tumor, although 3 of 5 carriers developed thyroid alterations. We provide functional evidence supporting the pathogenicity of a novel in-frame deletion. A 56-year-old woman with ovarian carcinoma and toxic diffuse thyroid hyperplasia was found to have a postzygotic hotspot missense variant.

Conclusion

The prevalence of DICER1 pathogenic variants in cancer predisposition populations was 5 to 6 times that reported in the general population. Pediatric-onset DTPS is well characterized, whereas adult carriers mainly present with thyroid abnormalities in the absence of DICER1-related family history, thus requiring accurate criteria for its identification when in constellation with other tumor types. Postzygotic hotspot missense variants may exist without the expected severe phenotype.
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来源期刊
Genetics in Medicine
Genetics in Medicine 医学-遗传学
CiteScore
15.20
自引率
6.80%
发文量
857
审稿时长
1.3 weeks
期刊介绍: Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.
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