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
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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