GLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions.

TitleGLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions.
Publication TypeJournal Article
Year of Publication2023
AuthorsJessurun J, Orr C, McNulty SN, Hagen CE, Alnajar H, Wilkes D, Kudman S, Assaad MAl, Dorsaint P, Ohara K, He F, Chiu K, Yin YMei, Xiang JZhaoying, Qin L, Sboner A, Elemento O, Yantiss RK, Graham RP, Poizat F, Mosquera JMiguel
JournalAm J Surg Pathol
Date Published2023 Jan 01
KeywordsAged, 80 and over, Biomarkers, Tumor, Female, Fibroma, Gastrointestinal Neoplasms, Gene Fusion, Humans, In Situ Hybridization, Fluorescence, Intestine, Small, Male, Middle Aged, Neoplasm Recurrence, Local, S100 Proteins, Soft Tissue Neoplasms, Young Adult, Zinc Finger Protein GLI1

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions. We studied three unique mesenchymal small bowel tumors. Paraffin embedded tumor tissues from these cases and 62 additional tumor samples that included a plexiform fibromyxoma were sequenced using a targeted RNAseq method to detect fusion events. The study patients included two women and one man who were 52, 80, and 22 years of age at the time of diagnosis. The tumors involved the submucosa and muscularis propria of the duodenum, jejunum, and ileum. All 3 tumors contained a proliferation of monotonous oval or spindle cells with scattered, somewhat dilated vessels. Two cases showed epithelioid structures such as glands, tubules, or nests. Immunohistochemical analysis revealed cytokeratin expression in the epithelioid components of both tumors displaying these features, and variable numbers of mesenchymal cells. Diffuse CD56 positivity was seen in the mesenchymal component of 2 tumors and desmin and smooth muscle actin staining in the other tumor. Immunostains for S-100 protein, DOG-1, and CD117 were negative in all cases. GLI1 fusions with different partner genes were detected in all tumors, and in the plexiform fibromyxoma, used as a control. Validation by fluorescence in situ hybridization was performed. None of the tumors have recurred or metastasize after surgery. We describe novel GLI1 fusions in 3 mesenchymal neoplasms of the small intestine, including 2 with biphenotypic features. Thus far, all cases have pursued indolent clinical courses. We propose the term " GLI1 -rearranged enteric tumor" to encompass this group of unique neoplasms of the small intestine that harbor GLI1 gene fusions and expand the spectrum of gastrointestinal neoplasms with these alterations.

Alternate JournalAm J Surg Pathol
PubMed ID35968961
Related Faculty: 
Jose Jessurun, M.D. Juan Miguel Mosquera, M.D. Andrea Sboner, Ph.D.

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