期刊论文详细信息
The oncologist
FGFR2 -Altered Gastroesophageal Adenocarcinomas Are an Uncommon Clinicopathologic Entity with a Distinct Genomic Landscape
article
Samuel J. Klempner1  Farshid Dayyani3  Daniel V.T. Catenacci4  Jeeyun Lee5  Joseph Chao6  Russell Madison7  Vivek Pujara1  Jeffrey S. Ross7  Vincent A. Miller7  Siraj M. Ali7  Alexa B. Schrock7  Seung Tae Kim5  Steven B. Maron9 
[1] The Angeles Clinic and Research Institute;Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute;Division of Hematology-Oncology, Department of Medicine, University of California Irvine;Department of Medicine, Division of Hematology-Oncology, University of Chicago School of Medicine;Samsung Medical Center, Sungkyunkwan University School of Medicine;Department of Developmental Therapeutics, City of Hope Comprehensive Cancer Center;Foundation Medicine, Inc.;Upstate Medical University;Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center
关键词: Fibroblast growth factor receptor 2;    Gastric cancer;    Gastroesophageal junction adenocarcinoma;    Heterogeneity;    Receptor tyrosine kinase;   
DOI  :  10.1634/theoncologist.2019-0121
学科分类:地质学
来源: AlphaMed Press Incorporated
PDF
【 摘 要 】

Background With the exception of trastuzumab, therapies directed at receptor tyrosine kinases (RTKs) in gastroesophageal adenocarcinomas (GEA) have had limited success. Recurrent fibroblast growth factor receptor 2 (FGFR2) alterations exist in GEA; however, little is known about the genomic landscape of FGFR2 -altered GEA. We examined FGFR2 alteration frequency and frequency of co-occurring alterations in GEA. Subjects, Materials, and Methods A total of 6,667 tissue specimens from patients with advanced GEA were assayed using hybrid capture-based genomic profiling. Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA, and microsatellite instability was determined on 95 or 114 loci. Descriptive statistics were used to compare subgroups. Results We identified a total of 269 (4.0%) FGFR2 -altered cases consisting of FGFR2 -amplified (amp; 193, 72% of FGFR2 -altered), FGFR2 -mutated (36, 13%), FGFR2 -rearranged (re; 23, 8.6%), and cases with multiple FGFR2 alterations (17, 6.3%). Co-occurring alterations in other GEA RTK targets including ERBB2 (10%), EGFR (8%), and MET (3%) were observed across all classes of FGFR2-altered GEA. Co-occurring alterations in MYC (17%), KRAS (10%), and PIK3CA (5.6%) were also observed frequently. Cases with FGFR2amp and FGFR2re were exclusively microsatellite stable. The median TMB for FGFR2 -altered GEA was 3.6 mut/mb, not significantly different from a median of 4.3 mut/mb seen in FGFR2 wild-type samples. Conclusion FGFR2 -altered GEA is a heterogenous subgroup with approximately 20% of FGFR2 -altered samples harboring concurrent RTK alterations. Putative co-occurring modifiers of FGFR2-directed therapy including oncogenic MYC, KRAS , and PIK3CA alterations were also frequent, suggesting that pretreatment molecular analyses may be needed to facilitate rational combination therapies and optimize patient selection for clinical trials. Implications for Practice Actionable receptor tyrosine kinase alterations assayed within a genomic context with therapeutic implications remain limited to HER2 amplification in gastroesophageal adenocarcinomas (GEA). Composite biomarkers and heterogeneity assessment are critical in optimizing patients selected for targeted therapies in GEA. Comprehensive genomic profiling in FGFR2 -altered GEA parallels the heterogeneity findings in HER2 -amplified GEA and adds support to the utility of genomic profiling in advanced gastroesophageal adenocarcinomas.

【 授权许可】

CC BY|CC BY-NC   

【 预 览 】
附件列表
Files Size Format View
RO202108130000343ZK.pdf 1066KB PDF download
  文献评价指标  
  下载次数:0次 浏览次数:1次