TACC2 (Transforming Acidic Coiled-Coil Containing Protein 2)

Comprehensive genomic profiling (CGP) identified FGFR2-TACC2 fusion, TP53 mutation, and Rb1 loss. These findings suggest that targeted therapy may be considered in such rare and aggressive variants.

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target.

The independent prognostic factors identified in this study provide a theoretical basis for individualized prognosis judgment in OCCC and HGSC. The SMGs and TMB levels may serve as valuable indicators for prognosis and evaluating targeted therapy or immunother-apy efficacy. Druggable genes such as NOTCH1 and RYR3 offer promising therapeutic tar-gets, while stage-specific pathway enrichments reveal potential intervention strategies. Further validation in larger cohorts is needed to confirm these findings. Our study advances the under-standing of molecular heterogeneity in ovarian cancer and lays the groundwork for personal-ized treatment strategies, ultimately improving patient outcomes.

Moreover, EphA2 inhibitors dasatinib and ALW II-41-27 remarkably suppress the progression of tumors expressing PLEKHA1-TACC2 in vivo. Functionally, PLEKHA1-TACC2 fusion and Trp53 deletion significantly increases tumor incidence, tumor multiplicity, and mouse mortality in transgenic ESCC mouse model, which could be suppressed by regorafenib, a EphA2 inhibitor approved by FDA in solid tumors. Together, our data indicate that PLEKHA1-TACC2 fusion protein has oncogenic activities and serves as a promising prognosis marker and therapeutic target.

In conclusion, TACC2 is an important regulator of the immune response in STS, functioning as a tumor suppressor and a modulator of response to PD-1 blockade. Its role in modulating chemokine expression and CD8 + T cell infiltration highlights its potential as a therapeutic target and predictive biomarker for STS immunotherapy.

P2, N=316, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Mar 2025 --> Dec 2025

The findings suggest a strategy for cancer treatment based on synthetic lethality.

We genotyped SVs at allele resolution, identifying genes (Rgs6, Dpf3 and Tacc2) crucial for maintaining ALT telomere stability. Our genome assembly-based approach elucidated the unique characteristics of ALT genome, offering insights into the genome evolution of cells surviving telomere-derived crisis.

FHNC include a morphological spectrum of carcinomas with squamous features and may occur in different HN locations, such as parotid gland and the sinonasal tract. Sinonasal cases can harbour FGFR2 rearrangement with or without associated high-risk HPV. Timely recognition of FHNC could help select patients potentially amenable to targeted therapy with FGFR inhibitors. Further studies are needed (1) to determine if FGFR2 rearranged/HPV-positive sinonasal carcinomas are biologically distinct from HMSC, and (2) to elucidate the biological and clinical significance of FGFR2 rearrangement in the context of high-risk HPV.

This study can improve our understanding of the mechanisms underlying the pathophysiology and post-infection sequelae of mpox. Our findings provide valuable insights into the various modes of MPV infection.

Our results offer novel insights into the genomic landscape and clonal trajectory of AML with abn(7). This work unravels formerly underestimated genetic lesions (KMT2Cmut) and alterations with high prognostic impact (abnTP53 and IDH2mut) for better future risk stratification.