GLI1 Gene Alterations in Neoplasms of the Genitourinary and Gynecologic Tract.
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 05 2022
01 05 2022
Historique:
pubmed:
16
12
2021
medline:
20
4
2022
entrez:
15
12
2021
Statut:
ppublish
Résumé
We report 4 neoplasms of the kidney (2 cases) and uterus (2 cases) harboring rearrangements or amplifications of the GLI1 gene, which because of their unusual clinical presentation, morphology, and immunoprofile mimicked other neoplasms, causing significant diagnostic challenge. The neoplasms occurred in 4 female patients ages 33 to 88 years. Histologically they all demonstrated nodular growth, solid architecture, bland epithelioid to ovoid-spindle cells with pale cytoplasm set in a variably myxoid or hyalinized stroma. One uterine tumor also demonstrated a focal round cell pattern, while another demonstrated focal pleomorphism. Unlike most previously reported neoplasms with these genetic abnormalities, the neoplasms in the current series were negative for S100 protein and minimally reactive for actin. All labeled for CD10 and cyclin D1, while 2 labeled for estrogen receptor and BCOR and 1 labeled for desmin, raising consideration of endometrial stromal sarcoma, myxoid leiomyosarcoma, metastatic breast carcinoma, and glomus tumor. One renal neoplasm demonstrated a GLI1-FOXO4 gene fusion and the other harbored a GLI1 gene rearrangement (unknown partner). The 2 uterine neoplasms exhibited GLI1 gene amplifications. GLI1-altered neoplasms (particularly those with GLI1 amplification) show variable morphology and lack a consistent immunophenotype, and thus may trigger diagnostic challenges which can be resolved by molecular testing.
Identifiants
pubmed: 34907995
doi: 10.1097/PAS.0000000000001844
pii: 00000478-202205000-00010
pmc: PMC9018467
mid: NIHMS1756331
doi:
Substances chimiques
Biomarkers, Tumor
0
GLI1 protein, human
0
Zinc Finger Protein GLI1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
677-687Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA140146
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217694
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: Supported in part by P50 CA 217694 (CRA), P50 CA 140146-01 (CRA), P30 CA 008748 (CRA); Cycle for Survival (CRA), Kristin Ann Carr Foundation (CRA), Dahan Translocation Carcinoma Fund and Joey’s Wings (PA). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article
Références
Timmis AJ, Riobo-Del, Galdo NA. Another twist to the GLI code. Biochem J. 2020;477:4343–4347.
Chetty R. Gene of the month: GLI-1. J Clin Pathol. 2020;73:228–230.
Katoh M. Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers. Clin Sci (Lond). 2019;133:953–970.
Dahlen A, Fletcher CD, Mertens F, et al. Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms: pericytoma with t(7;12). Am J Pathol. 2004;164:1645–1653.
Dahlen A, Mertens F, Mandahl N, et al. Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12). Biochem Biophys Res Commun. 2004;325:1318–1323.
Bridge JA, Sanders K, Huang D, et al. Pericytoma with t(7;12) and ACTB-GLI1 fusion arising in bone. Hum Pathol. 2012;43:1524–1529.
Castro E, Cortes-Santiago N, Ferguson LM, et al. Translocation t(7;12) as the sole chromosomal abnormality resulting in ACTB-GLI1 fusion in pediatric gastric pericytoma. Hum Pathol. 2016;53:137–141.
Antonescu CR, Agaram NP, Sung YS, et al. A distinct malignant epithelioid neoplasm with GLI1 gene rearrangements, frequent S100 protein expression, and metastatic potential: expanding the spectrum of pathologic entities with ACTB/MALAT1/PTCH1-GLI1 fusions. Am J Surg Pathol. 2018;42:553–560.
Miettinen M, Makhlouf HR, Sobin LH, et al. Plexiform fibromyxoma: a distinctive benign gastric antral neoplasm not to be confused with a myxoid GIST. Am J Surg Pathol. 2009;33:1624–1632.
Spans L, Fletcher CD, Antonescu CR, et al. Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 up-regulation define a subset of plexiform fibromyxoma. J Pathol. 2016;239:335–343.
Graham RP, Nair AA, Davila JI, et al. Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene. Mod Pathol. 2017;30:1443–1452.
Xu B, Chang K, Folpe AL, et al. Head and neck mesenchymal neoplasms with GLI1 gene alterations: a pathologic entity with distinct histologic features and potential for distant metastasis. Am J Surg Pathol. 2020;44:729–737.
Agaram NP, Zhang L, Sung YS, et al. GLI1-amplifications expand the spectrum of soft tissue neoplasms defined by GLI1 gene fusions. Mod Pathol. 2019;32:1617–1626.
Pettus JR, Kerr DA, Stan RV, et al. Primary myxoid and epithelioid mesenchymal tumor of the kidney with a novel GLI1-FOXO4 fusion. Genes Chromosomes Cancer. 2021;60:116–122.
Koh NWC, Seow WY, Lee YT, et al. Pericytoma with t(7;12): the first ovarian case reported and a review of the literature. Int J Gynecol Pathol. 2019;38:479–484.
Kerr DA, Pinto A, Subhawong TK, et al. Pericytoma with t(7;12) and ACTB-GLI1 fusion: reevaluation of an unusual entity and its relationship to the spectrum of GLI1 fusion-related neoplasms. Am J Surg Pathol. 2019;43:1682–1692.
Smith NE, Illei PB, Allaf M, et al. t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases. Am J Surg Pathol. 2014;38:604–614.
Argani P, Reuter VE, Kapur P, et al. Novel MEIS1-NCOA2 gene fusions define a distinct primitive spindle cell sarcoma of the kidney. Am J Surg Pathol. 2018;42:1562–1570.
Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23:703–713.
Antonescu CR, Zhang L, Chang NE, et al. EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer. 2010;49:1114–1124.
Niewiadomski P, Niedziolka SM, Markiewicz L, et al. Gli proteins: regulation in development and cancer. Cells. 2019;8:147.
Mosquera JM, Sboner A, Zhang L, et al. Novel MIR143-NOTCH fusions in benign and malignant glomus tumors. Genes Chromosomes Cancer. 2013;52:1075–1087.
Hung YP, Fletcher CDM. Myopericytomatosis: clinicopathologic analysis of 11 cases with molecular identification of recurrent PDGFRB alterations in myopericytomatosis and myopericytoma. Am J Surg Pathol. 2017;41:1034–1044.
Miettinen M. Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis. Mod Pathol. 2014;27(suppl 1):S17–S29.
Rakha EA, Quinn CM, Foschini MP, et al. Metaplastic carcinomas of the breast without evidence of epithelial differentiation: a diagnostic approach for management. Histopathology. 2021;78:759–771.
Carter MR, Hornick JL, Lester S, et al. Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases. Am J Surg Pathol. 2006;30:300–309.
Kao YC, Sung YS, Zhang L, et al. BCOR overexpression is a highly sensitive marker in round cell sarcomas with BCOR genetic abnormalities. Am J Surg Pathol. 2016;40:1670–1678.
Brahmi M, Franceschi T, Treilleux I, et al. Molecular classification of endometrial stromal sarcomas using RNA sequencing defines nosological and prognostic subgroups with different natural history. Cancers (Basel). 2020;12:2604.
Arias-Stella JA III, Benayed R, Oliva E, et al. Novel PLAG1 gene rearrangement distinguishes a subset of uterine myxoid leiomyosarcoma from other uterine myxoid mesenchymal tumors. Am J Surg Pathol. 2019;43:382–388.
Dusek CO, Hadden MK. Targeting the GLI family of transcription factors for the development of anti-cancer drugs. Expert Opin Drug Discov. 2021;16:289–302.