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Genetic risk factors for gestational trophoblastic neoplasia - an International Study Group on Trophoblastic Diseases

Grant number: 18/11918-2
Support Opportunities:Research Grants - Visiting Researcher Grant - International
Duration: October 03, 2018 - October 12, 2018
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Izildinha Maestá
Grantee:Izildinha Maestá
Visiting researcher: Kevin Meyer Elias
Visiting researcher institution: Harvard University, Cambridge, United States
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Background: Complete molar pregnancies result after an abnormal fertilization event, leading to the development of placental tissue without the presence of a fetus. It is widely assumed that the development of gestational trophoblastic neoplasia (GTN) is biologically predetermined and intrinsic to complete hydatidiform mole (CHM). However, the underlying genetic mechanisms are still unclear. Objectives: To determine whether single nucleotide polymorphism (SNP) analysis is useful to identify genetic predisposition to post-CHM GTN. Methods: This multicentric study will include patients with complete hydatidiform mole who undergo molar evacuation at the four Trophoblastic Disease Reference Centers (New England Trophoblastic Disease Center and three Trophoblastic Disease Reference Centers in the State of São Paulo) from 2018 to 2020. All participating centers are integrated into the International Study Group on Trophoblastic Diseases, Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, Boston (MA). Clinical data will be collected including patient age, gestational age, gravidity, parity, pre-evacuation hCG titer, and molar outcome (remission/GTN development). Response to chemotherapy will be evaluated with reference to serial human chorionic gonadotropin (hCG) levels in patient serum, as a gold standard. Fresh molar tissue and buffy coat (leukocyte-enriched fraction of whole blood) samples from study participants and their partners will be collected, after obtaining informed consent. Samples will be de-identified to ensure confidentiality of patient information. Complete mole diagnosis will be confirmed by H&E section histopathological analysis and p57(KIP2) immunohistochemistry staining. DNA will be extracted from the molar tissue and buffy coat using a commercially available kit (Qiagen, Valencia, CA, EUA) according to the manufacturer's instructions. DNA quantification will be performed using Nanodrop instrument (Thermo Fisher, Wilminton, DE, EUA). Subsequently, 250 ng of high quality DNA will be hybridized using Affymetrix Cytoscan 750K array (Affymetrix, Santa Clara, CA, EUA) according to the manufacturer's protocol. The haplotypes of the samples will be compared to reference genomes provided by the HapMap project. Any potential markers will be validated using archival material from Brigham Women´s Hospital. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MAESTA, IZILDINHA; DE FREITAS SEGALLA MOREIRA, MARJORY; REZENDE-FILHO, JORGE; BIANCONI, MARIA INES; JANKILEVICH, GUSTAVO; OTERO, SILVINA; CORREA RAMIREZ, LUZ ANGELA; SUN, SUE YAZAKI; ELIAS, KEVIN; HOROWITZ, NEIL; et al. Outcomes in the management of high-risk gestational trophoblastic neoplasia in trophoblastic disease centers in South America. International Journal of Gynecological Cancer, v. 30, n. 9, p. 6-pg., . (18/11918-2)

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