Anti-FGF12 (aa 1-168) polyclonal antibody

Background The prognostic factors for early-stage nonsmall cell lung cancers (NSCLCs) are not well defined. This study aimed to investigate the effect of highly frequent mutations on the outcomes patients with early-stage NSCLC, particularly those with surgically resected stage I disease. Methods The Cancer Genome Atlas (TCGA) datasets for Lung Adenocarcinoma (LUAD), Lung Squamous Cell Carcinoma (LUSC), and Pan-Lung Cancer (PLC) were accessed via cBioportal and searched to identify patients with stage I NSCLC. We identified candidate genes with a high (>10%) frequency of mutations and copy-number alterations and examined their effect on overall survival (OS) and disease-free survival (DFS). The details of clinicopathologic features were analyzed with the Fisher's exact? Mann-WhitneyUtest and Cox regression analysis. Survival was analyzed with Kaplan-Meier curves, and differences were compared with the log-rank and chi-square test. Results We identified 408 patients with stage I NSCLC from the PLC dataset. Of the 41 candidate genes with high-frequency mutation rates, six genes were significantly associated with OS:TP53,LPP,MAP3K13,FGF12,BCL6, andTP63. Further stratified analysis in PLC, LUAD, and LUSC datasets, we only identified thatTP53was significantly associated with OS in patients with surgically resected stage I lung adenocarcinoma. Conclusions TP53mutations are potentially markers of poor prognosis for stage I lung adenocarcinoma patients. The mutation status of this gene may contribute to clinical decision-making with respect to selecting patients who may benefit from adjuvant therapy.

Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report.