Genomic profile in gestational and non-gestational choriocarcinomas.
Gestational (GC) (derived from the placenta) and non-gestational (NGC) choriocarcinomas are trophoblastic diseases originated from abnormal proliferation of trophoblastic cells. These rare tumors share similar morphology and pathological features and differ on chemotherapy response, genetic origin and prognosis. In this study, the genomic profile of choriocarcinomas was performed according to their origin (GC or NGC) aiming to better understand these poorly characterized diseases.



Thirteen patients were included in this study; 10 presented previous history of hydatidiform mole and six developed metastasis. Twelve polymorphic microsatellite markers (D15S659, APOC2, D5S816, BAT25, D3S1614, D3S1311, D1S1656, APC-D5S346, D3S1601, D18S70, D8S1110 and D11S1999) were investigated to distinguish GC from NGC. All choriocarcinomas were evaluated by copy number alterations using array CGH.



Eight cases were classified as GC and five as NGC. Although potentially polymorphic, NGC exhibited significant gain of 21p11. Rare copy number alterations (CNA) were detected as a frequent event in GC including gains of 1p36.33-p36.32 (3 cases), 17q25.3 (4 cases), and losses of 9q33.1 (5 cases), 17q21.3 (3 cases) and 18q22.1 (4 cases) (varying from 724 to 3,053 Kb).



Two tumor suppressor genes are candidates to be involved in GC: TRIM32 (9q33.1) and CDH19 (18q22.1). Gains of CBX2, CBX4 and CBX8 were frequently found in high risk prognostic score in GC. The in silico functional interaction analysis revealed the involvement of PTEN and PI3K-Akt signaling pathways. These data pointed out significant genomic alterations in GC, opening new avenues to better characterize the pathobiology of this disease.
International Research Center - AC Camargo Cancer Center, São Paulo, SP, Brazil.
Julia Bette Homem de
JB
Mello
Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
Priscila Daniele
PD
Ramos Cirilo
Dept de Oncologia Clínica, Faculdade de Medicina, UNESP - Botucatu, SP, Brazil.
Odair Carlito
OC
Michelin
Dept de Patologia, Faculdade de Medicina, UNESP - Botucatu, SP, Brazil.
Maria Aparecida
MA
Custódio Domingues
Dept de Ginecologia e Obstetrícia, Faculdade de Medicina, UNESP - Botucatu, SP, Brazil.
Marilza Vieira
MV
Cunha Rudge
Dept de Urologia, Faculdade de Medicina, UNESP -Botucatu, SP, Brazil; Department of Clinical Genetics, Vejle Sygehus and Institute of Regional Health, University of Southern Denmark, Vejle, Denmark. Electronic address: silvia.regina.rogatto@rsyd.dk.
Silvia Regina
SR
Rogatto
Dept de Ginecologia e Obstetrícia, Faculdade de Medicina, UNESP - Botucatu, SP, Brazil.
Izildinha
I
Maestá
D000293:Adolescent; D000328:Adult; D002822:Choriocarcinoma / Q000235:genetics* / Q000473:pathology; D031954:Choriocarcinoma, Non-gestational / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D005260:Female; D023281:Genomics; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
Array comparative genomic hybridization; Copy number alteration; Gestational choriocarcinoma; Microsatellites; Non-gestational choriocarcinoma