GRM1 overexpression

Case 1: 73-year-old woman, January 2014 retroperitoneal leiomyosarcoma of the ureter - R0 en bloc resection with partial resection of the ureter and left hemicolectomy - Transcriptome-guided adjuvant treatment: Sorafenib and Riluzole due to GRM1 gene overexpression - Scapular recurrence with bone infiltration in Sept...Treatment with Tazemetostat in December 2022...- Neoadjuvant chemotherapy and radiotherapy treatment, R0 wide surgery with adequate preservation of functionality and IORT - Early chest wall dermal/subcutaneous recurrence (resected) after initiation of immunotherapy – Nivolumab – due to a favorable profile for immunotherapy in tumor transcriptome - Genome of recurrence: BRAF V600E mutation. Treatment with Dabrafenib + Trametinib... STS are tumors with complex surgical and oncological management and a poor response to conventional chemotherapy protocols. Given its heterogeneity, precision oncology through molecular profiling with next-generation massive sequencing (panels for tumor genome and transcriptome) allows the development of personalized therapeutic strategies in patients with STS, and opens up the possibilities for targeted treatments for molecular alterations, immunotherapy and the development of new agents.

Both melanomas rapidly developed visceral metastases following diagnosis, with a fatal outcome in one case and tumor progression under palliative care in the other case. This data suggests that GRM1 gene fusions could represent an additional rare oncogenic driver in the setting of blue nevi, mutually exclusive of classical canonical mutations, especially in plaque-type or Ota subtypes.

GRM1 immunohistochemistry was negative (<5%) in histologic mimics of CMF, including conventional chondrosarcoma, enchondroma, chondroblastoma, clear cell chondrosarcoma, giant cell tumor of the bone, fibrous dysplasia, chondroblastic osteosarcoma, myoepithelial tumor, primary aneurysmal bone cyst, brown tumor, phosphaturic mesenchymal tumor, CMF-like osteosarcoma, and extraskeletal myxoid chondrosarcoma. These results indicate that GRM1 immunohistochemistry may have utility in distinguishing CMF from its histologic mimics.