Genetic Landscape of Somatic Mutations in a Large Cohort of Sporadic Medullary Thyroid Carcinomas Studied by Next-Generation Targeted Sequencing

被引：144

作者：

Ciampi, Raffaele ^{[1
]}

Romei, Cristina ^{[1
]}

Ramone, Teresa ^{[1
]}

Prete, Alessandro ^{[1
]}

Tacito, Alessia ^{[1
]}

Cappagli, Virginia ^{[1
]}

Bottici, Valeria ^{[1
]}

Viola, David ^{[1
]}

Torregrossa, Liborio ^{[2
]}

Ugolini, Clara ^{[2
]}

Basolo, Fulvio ^{[2
]}

Elisei, Rossella ^{[1
]}

机构：

[1] Univ Hosp Pisa, Dept Clin & Expt Med, Unit Endocrinol, I-56124 Pisa, Italy

[2] Univ Hosp Pisa, Mol Pathol & Crit Area, Dept Surg Med, I-56124 Pisa, Italy

来源：

ISCIENCE | 2019年 / 20卷

关键词：

RET PROTOONCOGENE; RAS MUTATIONS; ACQUIRED-RESISTANCE; LOW-PREVALENCE; CANCER; HEREDITARY; MECHANISMS; PERCENTAGE; DIAGNOSIS; DOMAIN;

D O I：

10.1016/j.isci.2019.09.030

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Sporadic Medullary Thyroid Carcinoma (sMTC) is a rare but aggressive thyroid tumor. RET and RAS genes are present in about 50%-80% of cases, but most of the remaining cases are still orphan of a genetic driver. We studied the largest series of sMTC by deep sequencing to define the mutational landscape. With this methodology we greatly reduced the number of RET- or RAS-negative cases and we confirmed the central role of RET and RAS mutations. Moreover, we highlighted the bad prognostic role of RET mutations in sMTC and consolidated the favorable prognostic role of RAS mutations. For the first time, we showed that the variant allele frequency represents an additional prognostic marker inside the group of RET-mutated sMTC.

引用

页码：324 / +

页数：23

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