SEPTIN14 (Septin 14)

This study highlights poor survival outcomes in GBM patients with parietal lobe tumors. Key genetic alterations, such as PTEN mutations and fusion genes, drive tumor progression and chemoresistance in parietal lobe tumors. The association between radiomic features and survival indicates their potential as non-invasive prognostic biomarkers, which could aid in personalized treatment and improved patient management.

Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial's primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.

We identified ROS1 fusions (CEP85L-ROS1 and GOPC-ROS1) in 8% of samples, and those might be targeted by crizotinib analogs...Next, we measured cfDNA levels in vitro in response to Temozolomide treatment and discovered a positive correlation between unique 2000bp cfDNA fragments (R=0.8961, P-value=0.015632) and treatment responses in vitro... cfDNA may be used for the detection of exclusive patient mutations and gene fusions and is an emerging diagnostic tool in GBM.

We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68% of patients with GC harbor potential targetable gene fusions, which were enriched in patients with ERBB2 amplification. Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.

Afatinib had modest activity in a cohort of heavily pretreated cancer pts harboring common and uncommon EGFR mutations and did not meet its primary endpoint. Further evaluation of EGFR exon 18 fusions in glioblastoma or other cancers may be of interest. NCT02465060 This study was coordinated by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under award numbers: U10CA180820, U10CA180794, UG1CA233302, UG1CA233180, UG1CA233341, and UG1CA233337.

Only 24 patients harbored one or more of these 30 fusions, and only two fusions were present in more than one patient: FGFR3::TACC3 and EGFR::SEPTIN14. This in silico study provides a good starting point for the identification of gene fusions with functional consequences in the pathogenesis or treatment of glioblastoma.

"The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates."

Given the existence of EGFR exon 19 deletions, erlotinib was implemented and achieved a short response for 10 months...Osimertinib combined bevacizumab, chemotherapy (carboplatin and abraxane) and dacomitinib were implemented in turn but ineffective. Thus, osimertinib combined intrathecal chemotherapy with pemetrexed were carried out and gained a complete remission of neurologic symptoms, stable lesions and long-term survival without notable side effects. This study presented the first case of NSCLC-LM harboring particular EGFR-SEPT14 fusions, who showed a durable response to osimertinib and intrathecal pemetrexed, providing a potential therapeutic option for NSCLC-LM patients with this particular mutation.

The EGFR-IGR fusion mutation is unreported, and thus, there are no studies targeting this fusion together with EGFR amplification in lung adenocarcinoma. Our brief study provides clinical evidence that combined targeted therapy with gefitinib and cetuximab could result in a significant antitumor response in patients with the EGFR-IGR fusion and EGFR amplification.

EGFR fusions were detected in 0.32% (29/9097) of our Chinese patients. EGFR-TKIs may be effective therapeutic options in tumors harboring EGFR fusions. Combined with the diverse distribution of EGFR fusion breakpoints and the high frequency of gene-intergenic/intergenic-gene fusion, a comprehensive analysis of EGFR fusions may require the support of multiple platforms.

ERBB gene fusions are detectable at low frequency in various tumor types and may represent a unique genomic subset of cancer . Identification of novel ERBB gene fusions warrants further investigation to determine the potential pathogenicity and actionability of these fusions.