Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma

Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma

The prognosis of <i>BRAF<sup>V600E</sup></i>-mutant papillary thyroid carcinoma (PTC) ranges from indolent to highly aggressive courses. To better define the genetic diversity of this subtype, we evaluated the survival according to the presence of an additional mutation in ge...

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Bibliographic Details
Main Authors: Eyun Song, Meihua Jin, Ahreum Jang, Min Ji Jeon, Dong Eun Song, Hye Jin Yoo, Won Bae Kim, Young Kee Shong, Won Gu Kim
Format: article
Language:EN
Published: MDPI AG 2021
Subjects:
papillary thyroid carcinoma
genetic mutation
BRAF
functional groups
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Online Access:https://doaj.org/article/a84d0ba8a0654c78b83d51e726ac5ecd
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Summary:The prognosis of <i>BRAF<sup>V600E</sup></i>-mutant papillary thyroid carcinoma (PTC) ranges from indolent to highly aggressive courses. To better define the genetic diversity of this subtype, we evaluated the survival according to the presence of an additional mutation in genes encoding functional groups (FGs) in <i>BRAF<sup>V600E</sup></i>-mutant advanced PTC patients. Targeted next-generation sequencing was performed in primary tumors of 50 <i>BRAF<sup>V600E</sup></i>-mutant PTCs with distant metastasis or aggressive variants. The mutation in genes encoding FGs included alterations in histone methyltransferases, SWI/SNF subunit, and the PI3K/AKT/mTOR pathway. The primary outcome was overall survival (OS). Fifteen patients only had the <i>BRAF<sup>V600E</sup></i>-mutation (group 1), 22 had <i>BRAF<sup>V600E</sup></i> and mutation other than FGs (group 2), and 13 had <i>BRAF<sup>V600E</sup></i> and FG mutation (group 3). OS was significantly lower in patients with FG mutations (<i>p</i> = 0.001) than those without, and group 3 patients had the worst survival (<i>p</i> = 0.004). OS significantly varied among none, one, or two FG mutation sites (<i>p</i> = 0.005). Presence of FG mutation was independently associated with increased mortality (hazard ratio 11.65, 95% confidence interval 1.39–97.58, <i>p</i> = 0.024). Coexistence of mutations in <i>BRAF<sup>V600E</sup></i> and genes encoding FGs was associated with high mortality. Identification of FG mutation in <i>BRAF<sup>V600E</sup></i>-mutant PTCs may be valuable in risk stratifying this subtype.

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