利用家族性全外显子组测序鉴定BCL2L11作为非髓样甲状腺癌遗传易感的候选基因

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Duygu Abbasoglu, Mathis Lepage, Nicolas Sonnier, Sandrine Viala, Nancy Uhrhammer, Flora Ponelle-Chachuat, Anne Cayre, Maud Privat, Mathias Cavaillé, Yannick Bidet
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引用次数: 0

摘要

家族性非髓样甲状腺癌,定义为两个或两个以上一级亲属受影响,占甲状腺癌的3%-9%。它与更具侵袭性的癌症、早期诊断、多灶性以及转移和复发的风险增加有关。虽然目前还没有发现高外显率的易感基因,但估计遗传学的贡献是显著的。本研究利用全外显子组测序技术对5个FNMTC家族进行了研究,发现了3个候选基因:一个家族的TELO2,另一个家族的UACA和BCL2L11。所有这些肿瘤抑制基因都在甲状腺中表达,在肿瘤组织中与健康组织相比,在硅和我们的样本中均表现出低表达,其中两个已知通过FOXO3A途径参与甲状腺癌的发生。在甲状腺癌细胞中验证这些候选基因的功能分析表明,其中一个候选基因BCL2L11对增殖和凋亡具有抑瘤作用。它们对甲状腺癌遗传易感性的影响,以及它们的综合效应,需要进一步研究。事实上,病例对照研究对于确定常规分析的诊断效用至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of BCL2L11 as a Candidate Gene for Hereditary Predisposition to Non-Medullary Thyroid Cancer Using Familial Whole-Exome-Sequencing.

Familial non-medullary thyroid cancer, defined as two or more affected first-degree relatives, accounts for 3%-9% of thyroid cancers. It is associated with more aggressive cancer, early age at diagnosis, multifocality, and increased risk of metastasis and recurrence. Although no high penetrance predisposing gene has been identified at present, the estimated contribution of genetics is significant. Our study explored five families presenting FNMTC using Whole-Exome Sequencing and found three candidate genes: TELO2 in one family, UACA and BCL2L11 in another. All of these tumor suppressor genes are expressed in the thyroid, exhibit under-expression in tumor tissue compared to healthy tissue both in silico and in our samples, and two of them are known to be involved in thyroid carcinogenesis via the FOXO3A pathway. Functional analysis to validate these candidate genes in thyroid cancer cells showed that one of the three, BCL2L11, has a tumor suppressor effect on proliferation and apoptosis. Their impact on hereditary predisposition to thyroid cancer, as well as their combined effects, requires further study. Indeed, a case-control study would be essential to determine the diagnostic utility of their routine analysis.

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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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