KIF5B-RET fusion

In conclusion, EBC samples provide a valuable, noninvasive medium for detecting clinically relevant and previously uncharacterized fusion transcripts in non-small cell lung cancer (NSCLC). The high concordance between EBC and tissue biopsies suggests that EBC could complement tissue biopsy for effective diagnosis and monitoring of NSCLC. These findings underscore the importance of comprehensive molecular profiling using multiple sample types to enhance diagnostic precision and optimize therapeutic outcomes in lung cancer management.

Notably, patients with c-RET had a better prognosis than those with s-RET (median TTF: NR versus 5.67 months, P=0.037, median OS: NR versus 9.83 months, P=0.047). In conclusion, pralsetinib-based therapy may be a potential strategy to overcome acquired RET fusion after resistance to EGFR/ALK-TKIs.

Of total cohort, 18 patients (72.0 %) underwent intrathecal pemetrexed (ITP), with a median survival time of 7.4 months (95.0 % confidence interval, 3.3-11.6) from the initiation of ITP to death...Our results highlight CSF cfDNA NGS's potential in LM resistance understanding and ITP efficacy prediction. MET CNG positively impacts survival for ITP recipients, whereas the coexistence of EGFR T790M and EGFR-independent resistance mechanisms leads to poor outcomes.

Of four patients with PD-L1 overexpression (>50%) one received pembrolizumab and the other three patients received pemetrexed, carboplatin, and pembrolizumab or camrelizumab. Fifteen patients received selective RET inhibitors (pralsetinib and selpercatinib), resulting in an ORR of 53.3% (8/15) and median PFS of 10.0 months (95% CI 5.2-14.9). ICIs for PD-L overexpression and treatment naive patients offer comparable benefits for RET fusion-positive NSCLC, warranting further investigation.

C-LCNEC with adenocarcinoma and squamous cell carcinoma is rare and highly aggressive cancer. Surgical resection and adjuvant chemotherapy with SCLC regimen may improve the disease-free survival and overall survival. The accumulation of similar cases will clarify the profile and management of the disease.

RET fusions were identified in multiple tumor types. With a higher median TMB and commonly MSI-H, RET fusion positive CRC may be a unique molecular subset of CRC.

This study revealed a unique immune landscape at the single-cell level in rare-mutant NSCLC undergoing neoadjuvant chemo-immunotherapy. These findings may have implications for the development of personalized therapeutic strategies for patients with rare mutations in locally advanced NSCLC.

7 studies were invalid for both ADN&RNA,in 5 for DNA, one for ARN and in two cases without CNV detection.T% median was 90%(mean 75.4%). Among patients with invalid results 10 were rebiopsied. Thirty two patients have no genomic aberrations (24.4%).Co-ocurring molecular alterations-rate was 47,5%.Molecular alterations in KRAS and EGFR genes were the most frequent identified in 37(33%) and 22(16%) cases respectively.

P2, N=86, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2023 --> Jul 2026 | Trial primary completion date: Jul 2023 --> Jul 2026

"This study revealed the comprehensive mutational landscape of advanced NSCLC through liquid biopsy, providing novel biomarkers for clinical diagnosis and targeted therapy mechanism studies."

RNA fusions such as TMPRSS13-TMPRSS13, SUPT6H-ESR1, PTPRK-RSPO3, and KIF5B-RET were investigated and fusion junctions were successfully determined. Gene partners from multiple fusion pairs (e.g., SUPT6H-ESR1 and KIF5B-RET) were found to have an oncogenic role in lung cancer. Mutations in KIF5B and RET genes were found to associate with poor survival in the TCGA dataset suggesting that the novel RNA fusions may also play an oncogenic role in lung cancer.

9.5% of our tumors have oncogenic fusions that may be clinically relevant, which suggests patients with advanced cancers should have comprehensive molecular profiling that includes RNA sequencing. Additional studies are needed to determine the function of the identified unclassified gene fusions to assess potential clinical significance. Table- Unclassified Fusions (number per total unclassified fusions)Tumor Type (Total Number of Samples Profiled)Fusion Positive samplesUnclassified FusionsProstate adenocarcinoma (89)8 (32%)BMPR1B-PDLIM5 (2 patients), CDC13-SUGCT, NIPBL-RAI14, TTC6-MIPOL1, NFIB-UBE3B, GALNT7-SPOCK3, TBCA-AP3B1Breast cancer (224)8 (32%)NIPBL-PIEZO1, ETV6-RINT1, PAK1-TEX14, PAK1-MMP20, PAK1-LOC101928896, TTC6-MIPOL1, BMPR1B-PDLIM5, CMTM8-OSBPL10Non-small cell lung cancer (751)4 (16%)PANX1-PRPF19 (2 patients), TTC6-MIPOL1, GALNT7-SMIM8Head and neck cancer (177)2 (8%)ETV6-DNAH14, TP53BP1-SND1Salivary gland tumor (22)1 (4%)NFIB-CHCHD7Pancreatic adenocarcinoma (186)1 (4%)CMTM8-GPD1LOvarian cancer (362)1 (4%)NIPBL-SLC1A3Total Number of Fusions25