Complexity of the Genetic Background of Oncogenesis in Ovarian Cancer-Genetic Instability and Clinical Implications

被引：7

作者：

Murawski, Marek ^{[1
]}

Jagodzinski, Adam ^{[1
]}

Bielawska-Pohl, Aleksandra ^{[2
]}

Klimczak, Aleksandra ^{[2
]}

机构：

[1] Wroclaw Med Univ, Clin Dept Gynecol & Obstet 1, PL-50367 Wroclaw, Poland

[2] Polish Acad Sci, Hirszfeld Inst Immunol & Expt Therapy, Lab Biol Stem & Neoplast Cells, PL-53114 Wroclaw, Poland

来源：

CELLS | 2024年 / 13卷 / 04期

关键词：

genetic instability; oncogenesis; ovarian cancer; RRSO; TP53; mutations; BRCA1; BRCA2; BRAF mutations; RAS mutations; ARID1A mutations; PIK3CA mutations; PTEN mutations; CTNNB1; c-myc amplification; CLEAR-CELL; PIK3CA MUTATION; FREQUENT MUTATIONS; PROTEIN EXPRESSION; ARID1A MUTATIONS; P53; RESTORATION; BRAF MUTATION; EARLY EVENT; MUTANT P53; CARCINOMA;

D O I：

10.3390/cells13040345

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ovarian cancer is a leading cause of death among women with gynecological cancers, and is often diagnosed at advanced stages, leading to poor outcomes. This review explores genetic aspects of high-grade serous, endometrioid, and clear-cell ovarian carcinomas, emphasizing personalized treatment approaches. Specific mutations such as TP53 in high-grade serous and BRAF/KRAS in low-grade serous carcinomas highlight the need for tailored therapies. Varying mutation prevalence across subtypes, including BRCA1/2, PTEN, PIK3CA, CTNNB1, and c-myc amplification, offers potential therapeutic targets. This review underscores TP53's pivotal role and advocates p53 immunohistochemical staining for mutational analysis. BRCA1/2 mutations' significance as genetic risk factors and their relevance in PARP inhibitor therapy are discussed, emphasizing the importance of genetic testing. This review also addresses the paradoxical better prognosis linked to KRAS and BRAF mutations in ovarian cancer. ARID1A, PIK3CA, and PTEN alterations in platinum resistance contribute to the genetic landscape. Therapeutic strategies, like restoring WT p53 function and exploring PI3K/AKT/mTOR inhibitors, are considered. The evolving understanding of genetic factors in ovarian carcinomas supports tailored therapeutic approaches based on individual tumor genetic profiles. Ongoing research shows promise for advancing personalized treatments and refining genetic testing in neoplastic diseases, including ovarian cancer. Clinical genetic screening tests can identify women at increased risk, guiding predictive cancer risk-reducing surgery.

引用

页数：16

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