Expression of DNA Methyltransferase 3B Isoforms Is Associated with DNA Satellite 2 Hypomethylation and Clinical Prognosis in Advanced High-Grade Serous Ovarian Carcinoma
Por:
Del Castillo Falconi, Victor M., Diaz-Chavez, Jose, Torres-Arciga, Karla, Luna-Maldonado, Fernando, Gudino-Gomez, Adriana A., Pedroza-Torres, Abraham, Castro-Hernandez, Clementina, Cantu de Leon, David, Herrera, Luis A.
Publicada:
1 nov 2022
Resumen:
Alterations in DNA methylation are critical for the carcinogenesis of
ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA
methyltransferase (DNMT), encodes for fifteen spliced protein products
or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with
functional consequences on catalytic activity. Abnormal expression of
DNMT3B isoforms is frequently observed in several types of cancer, such
as breast, lung, kidney, gastric, liver, skin, leukemia, and sarcoma.
However, the expression patterns and consequences of DNMT3B isoforms in
OC are unknown. In this study, we analyzed each DNMT and DNMT3B isoforms
expression by qPCR in 63 OC samples and their association with
disease-free survival (DFS), overall survival (OS), and tumor
progression. We included OC patients with the main histological subtypes
of EOC and patients in all the disease stages and found that DNMTs were
overexpressed in advanced stages (p-value < 0.05) and high-grade OC
(p-value < 0.05). Remarkably, we found DNMT3B1 overexpression in
advanced stages (p-value = 0.0251) and high-grade serous ovarian
carcinoma (HGSOC) (p-value = 0.0313), and DNMT3B3 was overexpressed in
advanced stages (p-value = 0.0098) and high-grade (p-value = 0.0004)
serous ovarian carcinoma (SOC). Finally, we observed that overexpression
of DNMT3B isoforms was associated with poor prognosis in OC and SOC.
DNMT3B3 was also associated with FDS (p-value = 0.017) and OS (p-value =
0.038) in SOC patients. In addition, the ovarian carcinoma cell lines
OVCAR3 and SKOV3 also overexpress DNMT3B3. Interestingly, exogenous
overexpression of DNMT3B3 in OVCAR3 causes demethylation of satellite 2
sequences in the pericentromeric region. In summary, our results suggest
that DNMT3B3 expression is altered in OC.
Filiaciones:
Del Castillo Falconi, Victor M.:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Diaz-Chavez, Jose:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Torres-Arciga, Karla:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Luna-Maldonado, Fernando:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Gudino-Gomez, Adriana A.:
Inst Nacl Med Genom, Periferico 4809, Mexico City, Mexico
Pedroza-Torres, Abraham:
Catedras CONACYT, Inst Nacl Cancerol, Mexico City, Mexico
Castro-Hernandez, Clementina:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Cantu de Leon, David:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Herrera, Luis A.:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCAN, Inst Invest Biomed, Unidad Invest Biomed & Canc, Ave San Fernando 22,Sect 16, Mexico City 14080, Mexico
Inst Nacl Med Genom, Periferico 4809, Mexico City, Mexico
Green Published, gold, All Open Access, Gold, Green
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