FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of Non-small Cell Lung Cancer
A partir d'échantillons tumoraux prélevés sur 1 328 patients atteints d'un cancer du poumon non à petites cellules, cette étude met en évidence une association entre des gènes de fusion impliquant FGFR et un ensemble de caractéristiques cliniques
Purpose-The FGFR3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer. To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics and treatment outcomes of patients who had non-small cell lung cancer (NSCLC) with or without FGFR fusions.
Experimental Design-Fourteen known FGFR fusion variants, including FGFR1, FGFR2 and FGFR3, were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and verified by direct sequencing in 1328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET and ROS1. Clinical characteristics including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival (RFS) and overall survival (OS) were collected.
Results-Of 1328 tumors screened, 2 (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared to the FGFR fusion negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, p<0.001), significantly associated with larger tumor (>3cm) (88.2%, 15 of 17 patients, p<0.001) and with a tendency to be more poorly differentiation (53.9%, 9 of 17 patients, p=0.095).
Conclusions-FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR targeted therapy which needs further clinical investigation.
Clinical Cancer Research , résumé, 2014