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Abstract：
Familial nonmedullary thyroid cancer (FNMTC) accounts for approximately 3%-9% of all thyroid cancers; however, the mechanisms underlying FNMTC remain unclear. Environmental and genetic (especially genetic mutation) factors may play important roles in FNMTC etiology, development, and pathogenesis.
Three affected members, including two first-degree relatives, and three healthy members of a family with FNMTC were studied. We performed whole-exome and targeted gene sequencing to identify gene mutations that may be associated with FNMTC pathogenesis. The results were analyzed using Exome Aggregation Consortium data and the Genome Aggregation Database and further validated using Sanger sequencing.
Of 28 pivotal genes with rare nonsynonymous mutations found, 7 were identified as novel candidate FNMTC pathogenic genes (ANO7, CAV2, KANK1, PIK3CB, PKD1L1, PTPRF, and RHBDD2). Among them, three genes (PIK3CB, CAV2, and KANK1) are reportedly involved in tumorigenesis through the PI3K/Akt signaling pathway.
We identified seven pathogenic genes in affected members of a family with FNMTC. The PI3K/Akt signaling pathway is thought to be closely related to the development of FNMTC, and three of the susceptibility genes identified herein are associated with this pathway. These findings expand our understanding of FNMTC pathogenesis and underscore PI3K/Akt pathology as a potential therapy target.
Three affected members, including two first-degree relatives, and three healthy members of a family with FNMTC were studied. We performed whole-exome and targeted gene sequencing to identify gene mutations that may be associated with FNMTC pathogenesis. The results were analyzed using Exome Aggregation Consortium data and the Genome Aggregation Database and further validated using Sanger sequencing.
Of 28 pivotal genes with rare nonsynonymous mutations found, 7 were identified as novel candidate FNMTC pathogenic genes (ANO7, CAV2, KANK1, PIK3CB, PKD1L1, PTPRF, and RHBDD2). Among them, three genes (PIK3CB, CAV2, and KANK1) are reportedly involved in tumorigenesis through the PI3K/Akt signaling pathway.
We identified seven pathogenic genes in affected members of a family with FNMTC. The PI3K/Akt signaling pathway is thought to be closely related to the development of FNMTC, and three of the susceptibility genes identified herein are associated with this pathway. These findings expand our understanding of FNMTC pathogenesis and underscore PI3K/Akt pathology as a potential therapy target.
摘要：
家族性非髓样甲状腺癌（FNMTC）约占所有甲状腺癌的3％-9％；然而，FNMTC的潜在机制仍不清楚.环境和遗传(尤其是基因突变)因素可能在FNMTC病因中发挥重要作用。发展,和发病机制。
三名受影响的成员，包括两个一级亲属,研究了FNMTC家庭的三个健康成员。我们进行了全外显子组和靶向基因测序，以鉴定可能与FNMTC发病机制相关的基因突变。使用外显子组聚集联盟数据和基因组聚集数据库分析结果,并使用Sanger测序进一步验证结果。
在发现的28个具有罕见非同义突变的关键基因中，7个被鉴定为新的候选FNMTC致病基因(ANO7、CAV2、KANK1、PIK3CB、PKD1L1,PTPRF,和RHBDD2）。其中,三个基因(PIK3CB，据报道，CAV2和KANK1）通过PI3K/Akt信号通路参与肿瘤发生。
我们在FNMTC家族的受影响成员中鉴定了七个致病基因。PI3K/Akt信号通路被认为与FNMTC的发生发展密切相关,和本文鉴定的三个易感基因与该途径相关。这些发现扩展了我们对FNMTC发病机制的理解，并强调了PI3K/Akt病理学作为潜在的治疗靶标。
三名受影响的成员，包括两个一级亲属,研究了FNMTC家庭的三个健康成员。我们进行了全外显子组和靶向基因测序，以鉴定可能与FNMTC发病机制相关的基因突变。使用外显子组聚集联盟数据和基因组聚集数据库分析结果,并使用Sanger测序进一步验证结果。
在发现的28个具有罕见非同义突变的关键基因中，7个被鉴定为新的候选FNMTC致病基因(ANO7、CAV2、KANK1、PIK3CB、PKD1L1,PTPRF,和RHBDD2）。其中,三个基因(PIK3CB，据报道，CAV2和KANK1）通过PI3K/Akt信号通路参与肿瘤发生。
我们在FNMTC家族的受影响成员中鉴定了七个致病基因。PI3K/Akt信号通路被认为与FNMTC的发生发展密切相关,和本文鉴定的三个易感基因与该途径相关。这些发现扩展了我们对FNMTC发病机制的理解，并强调了PI3K/Akt病理学作为潜在的治疗靶标。
