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在经靶向测序定义的流行病学低风险患者中,成纤维细胞生长因子家族异常作为头颈部鳞状细胞癌的一种假定驱动因素。

Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low-risk patient as defined by targeted sequencing.

作者信息

Tillman Brittny N, Yanik Megan, Birkeland Andrew C, Liu Chia-Jen, Hovelson Daniel H, Cani Andi K, Palanisamy Nallasivam, Carskadon Shannon, Carey Thomas E, Bradford Carol R, Tomlins Scott A, McHugh Jonathan B, Spector Matthew E, Brenner J Chad

机构信息

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan.

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.

出版信息

Head Neck. 2016 Apr;38 Suppl 1(Suppl 1):E1646-52. doi: 10.1002/hed.24292. Epub 2016 Feb 5.

Abstract

BACKGROUND

Targeted sequencing of patients with epidemiologically low-risk (ELR) head and neck squamous cell carcinoma (HNSCC) could help identify novel drivers or lost suppressors leading to precision medicine protocols and improved survival rates.

METHODS

A patient with ELR-HNSCC was selected for targeted sequencing. We then assessed next generation sequencing cohorts from the Oncomine Powertool Database, which contains pan-cancer data from The Cancer Genome Atlas (TCGA).

RESULTS

Targeted sequencing revealed fibroblast growth factor receptor-1 (FGFR1) amplifications as a putative driver of the patient's tumor. Patients with HNSCC from TCGA data demonstrated fibroblast growth factor (FGF) family mutations, rearrangements, or amplifications in over 35% of HNSCC cases, with a statistically significant higher frequency in African American populations. FGF alterations were unique from activating phosphatidylinositol 3-kinase (PIK3CA) mutations.

CONCLUSION

Together, these data suggest that FGF signaling may be critical for a subset of patients with HNSCC independent of other known pathways and provides rationale for leveraging patients with ELR-HNSCC to define molecular subsets of high-risk HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1646-E1652, 2016.

摘要

背景

对具有流行病学低风险(ELR)的头颈部鳞状细胞癌(HNSCC)患者进行靶向测序,有助于识别新的驱动因素或缺失的抑制因子,从而制定精准医疗方案并提高生存率。

方法

选择一名ELR-HNSCC患者进行靶向测序。然后,我们评估了来自Oncomine Powertool数据库的下一代测序队列,该数据库包含来自癌症基因组图谱(TCGA)的泛癌数据。

结果

靶向测序显示,成纤维细胞生长因子受体-1(FGFR1)扩增是该患者肿瘤的一个假定驱动因素。来自TCGA数据的HNSCC患者中,超过35%的病例存在成纤维细胞生长因子(FGF)家族突变、重排或扩增,在非裔美国人中频率具有统计学意义的更高。FGF改变与激活磷脂酰肌醇3激酶(PIK3CA)突变不同。

结论

总之,这些数据表明,FGF信号传导可能对一部分HNSCC患者至关重要(独立于其他已知途径),并为利用ELR-HNSCC患者来定义高危HNSCC的分子亚群提供了理论依据。© 2016威利期刊公司。《头颈》38:E1646-E1652,2016年。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/4844767/1b58c6a5054d/nihms763661f1.jpg

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