PI3K/AKT/mTOR通路
癌症研究
甲状腺乳突癌
蛋白激酶B
甲状腺癌
肿瘤科
医学
甲状腺
内科学
癌症
生物
甲状腺癌
生物信息学
遗传学
信号转导
作者
Θεοδώρα Παππά,Sara Ahmadi,Ellen Marqusee,Hannah Johnson,Matthew A. Nehs,Nancy L. Cho,Justine A. Barletta,Jochen H. Lorch,Gerard M. Doherty,Neal I. Lindeman,Erik K. Alexander,Iñigo Landa
标识
DOI:10.1158/1078-0432.ccr-21-0874
摘要
The extent to which routine genomic sequencing can identify relevant secondary genomic alterations among BRAFV600E -mutant papillary thyroid carcinoma (PTC) is unknown. Such markers would prove highly valuable for prognostic purposes.We reviewed clinicopathologic data of 225 patients with BRAFV600E -mutant PTC and integrated them with genomic data derived from targeted next-generation sequencing (NGS) on tumor specimens. We defined patient subgroups based on bona fide secondary oncogenic events (separate from BRAFV600E ) and compared their clinical features and outcomes with those without additional oncogenic alterations.Additional oncogenic alterations were identified in 16% of tumors. Patients in the "BRAF+additional mutations" group were more likely to be at high American Thyroid Association (ATA) risk of recurrence (48.6% vs. 17.6%; P = 0.0009), had larger baseline tumor (2.7 vs. 1.9 cm; P = 0.0005) and more advanced stage at presentation (14.3% vs. 1.1% stage 4; P < 0.0001). Importantly, over a 65-month follow-up, disease-specific mortality (DSM) was increased when additional mutations were identified (13.8% vs. 1.4% in the BRAF-only group; P = 0.005). Separately, we identified a subcluster of patients harboring oncogenic mutations in key effectors of the PI3K/AKT/mTOR pathway, which were independently associated with DSM (OR = 47.9; 95% confidence interval, 3.5-1,246.5; P = 0.0043).Identification of additional PIK3/AKT/mTOR alterations in patients with BRAFV600E -mutant PTC provides important and actionable prognostic risk stratification. These data support genomic profiling of PTC tumors to inform prognosis and clinical strategy.
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