LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth.
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 m...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/2bf13702df0b43e381666c65815dbd11 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:2bf13702df0b43e381666c65815dbd11 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:2bf13702df0b43e381666c65815dbd112021-12-02T20:05:32ZLPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth.1932-620310.1371/journal.pone.0250518https://doaj.org/article/2bf13702df0b43e381666c65815dbd112021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0250518https://doaj.org/toc/1932-6203Gestational 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.Gavin R OliverSofia Marcano-BonillaJonathan QuistEzequiel J TolosaEriko IguchiAmy A SwansonNicole L HoppmanTanya SchwabAshley SigafoosNaresh ProdduturiJesse S VossShannon M KnightJin ZhangNumrah FadraRaul UrrutiaMichael ZimmermanJan B EganAnthony G BilyeuJin JenEma VerasRema'a Al-SafiMatthew BlockSarah KerrMartin E Fernandez-ZapicoJohn K SchoolmeesterEric W KleePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0250518 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Gavin R Oliver Sofia Marcano-Bonilla Jonathan Quist Ezequiel J Tolosa Eriko Iguchi Amy A Swanson Nicole L Hoppman Tanya Schwab Ashley Sigafoos Naresh Prodduturi Jesse S Voss Shannon M Knight Jin Zhang Numrah Fadra Raul Urrutia Michael Zimmerman Jan B Egan Anthony G Bilyeu Jin Jen Ema Veras Rema'a Al-Safi Matthew Block Sarah Kerr Martin E Fernandez-Zapico John K Schoolmeester Eric W Klee LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| description |
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. |
| format |
article |
| author |
Gavin R Oliver Sofia Marcano-Bonilla Jonathan Quist Ezequiel J Tolosa Eriko Iguchi Amy A Swanson Nicole L Hoppman Tanya Schwab Ashley Sigafoos Naresh Prodduturi Jesse S Voss Shannon M Knight Jin Zhang Numrah Fadra Raul Urrutia Michael Zimmerman Jan B Egan Anthony G Bilyeu Jin Jen Ema Veras Rema'a Al-Safi Matthew Block Sarah Kerr Martin E Fernandez-Zapico John K Schoolmeester Eric W Klee |
| author_facet |
Gavin R Oliver Sofia Marcano-Bonilla Jonathan Quist Ezequiel J Tolosa Eriko Iguchi Amy A Swanson Nicole L Hoppman Tanya Schwab Ashley Sigafoos Naresh Prodduturi Jesse S Voss Shannon M Knight Jin Zhang Numrah Fadra Raul Urrutia Michael Zimmerman Jan B Egan Anthony G Bilyeu Jin Jen Ema Veras Rema'a Al-Safi Matthew Block Sarah Kerr Martin E Fernandez-Zapico John K Schoolmeester Eric W Klee |
| author_sort |
Gavin R Oliver |
| title |
LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| title_short |
LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| title_full |
LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| title_fullStr |
LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| title_full_unstemmed |
LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| title_sort |
lpcat1-tert fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/2bf13702df0b43e381666c65815dbd11 |
| work_keys_str_mv |
AT gavinroliver lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT sofiamarcanobonilla lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT jonathanquist lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT ezequieljtolosa lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT erikoiguchi lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT amyaswanson lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT nicolelhoppman lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT tanyaschwab lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT ashleysigafoos lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT nareshprodduturi lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT jessesvoss lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT shannonmknight lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT jinzhang lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT numrahfadra lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT raulurrutia lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT michaelzimmerman lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT janbegan lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT anthonygbilyeu lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT jinjen lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT emaveras lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT remaaalsafi lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT matthewblock lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT sarahkerr lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT martinefernandezzapico lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT johnkschoolmeester lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth AT ericwklee lpcat1tertfusionsareuniquelyrecurrentinepithelioidtrophoblastictumorsandpositivelyregulatecellgrowth |
| _version_ |
1718375470952611840 |