CRTC1 (CREB Regulated Transcription Coactivator 1)

In addition to detailing specific features of our case, we also discuss those differences that may help distinguish ACTG1::MITF fusions from other clear cell tumors. Considering the significant differences in clinical outcomes between these distinct classes of clear cell tumors, accurate distinction can significantly affect management options.

The absence of the common MEC-associated fusion gene may indicate a more aggressive clinical course. Further accumulation of cases with detailed molecular characterization is crucial to clarify the pathogenesis, behavior, and optimal management strategies for this rare entity.

Cancer surgery, radiotherapy, parotidectomy, neck dissection, chemotherapy, and cisplatin were the keywords of treatment...There have always been the common keywords such as pathology, tumor marker, immunohistochemistry, Ki-67, CRTC1, MAML2, gene fusion, and fluorescence in situ hybridization (FISH). This study for the first time elucidated the current scenario and scientometric characteristics of MEC, and would help in improving in reciprocal collaboration and provide helpful guidance for further research.

Recognition of gene fusion signatures not only enhances diagnostic precision but also opens avenues for targeted therapy in selected cases. Continued molecular investigation and case accumulation are necessary to validate the biological behavior and therapeutic implications of many of these newly recognized entities.

Increased awareness among dermatologists and dermatopathologists can promote timely recognition and accurate diagnosis. The goal is for the expanding body of knowledge on CMTCT to continue informing diagnosis, long-term management, and providing insight into prognosis.

Features suggestive of MEC include complex branched glandular structures and subtle cytologic atypia. We emphasize the importance of incorporating MAML2 molecular testing into diagnostic algorithms for accurate classification, particularly in challenging lesions with lymphoid-rich stroma.

Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.

Surgical resection is the main treatment, and diagnosis requires confirmation through histopathology, immunohistochemistry, and special staining. CRTC1-MAML2 fusion can also assist in diagnosis.

WGS in SGC is achievable in clinically relevant timeframes, providing genomic information for deeper understanding of disease pathophysiology, to clarify histologic subtype and can identify actionable genomic targets which may not be found through routine sequencing technologies. Further use of WGS has the potential to improve care for patients with SGC.

We identified novel MAML2 fusion partners, most of which likely represent passenger alterations, possibly arising from genomic instability or impaired p53 function. However, ATXN3::MAML2 fusions, previously reported in a pre-cancerous pancreatic disease case, may represent a pathogenic alteration warranting further investigation.

The efficacy of combined CRTC1 knockdown/overexpression and atezolizumab (anti-PD-L1) was tested in an LLC xenograft mouse model...These findings indicate that CRTC1 in tumor cells suppresses PD-L1-mediated anti-tumor immunity and promotes tumorigenesis via the Notch1/Akt signaling axis. Dual targeting of CRTC1 and PD-L1 demonstrates therapeutic synergy, suggesting CRTC1 pathway inhibition could optimize immunotherapy outcomes in NSCLC patients.