LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth
Autor: | Eriko Iguchi, Raul Urrutia, Eric W. Klee, Ashley N. Sigafoos, Michael Zimmerman, Jesse S. Voss, Sarah E. Kerr, Jin Zhang, Anthony G. Bilyeu, Amy A. Swanson, Jin Jen, Matthew S. Block, Tanya L. Schwab, Numrah Fadra, Shannon M. Knight, Jan B. Egan, Ema Veras, John K. Schoolmeester, Martin E. Fernandez-Zapico, Nicole L. Hoppman, Gavin R. Oliver, Naresh Prodduturi, Sofia Marcano-Bonilla, Rema'a Al-Safi, Jonathan Quist, Ezequiel J. Tolosa |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Oncogene Proteins
Fusion Trophoblastic Tumor Uterus Cancer Treatment Lung and Intrathoracic Tumors Cell Fusion Pregnancy Medicine and Health Sciences Gestational Trophoblastic Disease DNA extraction Telomerase Multidisciplinary Gestational trophoblastic disease Epithelioid Cells 1-Acylglycerophosphocholine O-Acyltransferase Genomics Middle Aged medicine.anatomical_structure Oncology Uterine Neoplasms embryonic structures Medicine Female Research Article Adult Cell Physiology Science Biology Trophoblastic Neoplasms Malignant Tumors Extraction techniques Downregulation and upregulation Diagnostic Medicine medicine Carcinoma Genetics Cancer Detection and Diagnosis Biomarkers Tumor Humans Placental site trophoblastic tumor Epithelioid Trophoblastic Tumor Cell Proliferation Trophoblast Biology and Life Sciences Cancers and Neoplasms Cell Biology medicine.disease Research and analysis methods Cancer research |
Zdroj: | PLoS ONE, Vol 16, Iss 5, p e0250518 (2021) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Gestational trophoblastic disease (GTD) is a heterogeneous group of lesions arising from placental tissue. Epithelioid trophoblastic tumor (ETT), derived from chorionic-type trophoblast, is the rarest form of GTD with only approximately 130 cases described in the literature. Due to its morphologic mimicry of epithelioid smooth muscle tumors and carcinoma, ETT can be misdiagnosed. To date, molecular characterization of ETTs is lacking. Furthermore, ETT is difficult to treat when disease spreads beyond the uterus. Here using RNA-Seq analysis in a cohort of ETTs and other gestational trophoblastic lesions we describe the discovery of LPCAT1-TERT fusion transcripts that occur in ETTs and coincide with underlying genomic deletions. Through cell-growth assays we demonstrate that LPCAT1-TERT fusion proteins can positively modulate cell proliferation and therefore may represent future treatment targets. Furthermore, we demonstrate that TERT upregulation appears to be a characteristic of ETTs, even in the absence of LPCAT1-TERT fusions, and that it appears linked to copy number gains of chromosome 5. No evidence of TERT upregulation was identified in other trophoblastic lesions tested, including placental site trophoblastic tumors and placental site nodules, which are thought to be the benign chorionic-type trophoblast counterpart to ETT. These findings indicate that LPCAT1-TERT fusions and copy-number driven TERT activation may represent novel markers for ETT, with the potential to improve the diagnosis, treatment, and outcome for women with this rare form of GTD. |
Databáze: | OpenAIRE |
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