Developments in Genetics: Better Management of Ovarian Cancer Patients

Abstract

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing and to properly classify all ovarian cancers. In this article, we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels, details about the genes, and also candidate genes. We hope to bring new information to the medical field so as to better prevent and diagnose ovarian cancer.

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

“…They could be divided into two main subgroups of alternations: DNA repair-related genes (BRCA1/2, PTEN) and genes involved in cell signaling pathways as well as the cell cycle (PI3K/AKT/mTOR, RAS/MAPK). As mentioned above, the prevalence of these mutations varies across distinct subtypes of epithelial ovarian cancer [4][5][6]. TP53 mutations are predominant in high-grade serous ovarian cancer (HGSOC), with an increased mutation rate reaching 55%.…”

“…TP53, often referred to as "the guardian of the genome" or the "cellular gatekeeper", plays a crucial role in tumor suppression, being a checkpoint molecule. It achieves this by regulating the expression of downstream genes, triggering a range of cellular responses [6]. These responses include inducing cell cycle arrest or apoptosis in response to various types of stress, such as nutrient deprivation, telomere erosion, hypoxia, DNA damage, ribosomal stress, and oncogene activation [7][8][9][10].…”

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

“…Moreover, OC distinctly highlights how genetic and molecular dysregulations in the urogenital tract can lead to malignancy. Genetic mutations, notably in the BRCA1 and BRCA2 genes but also in TP53 , KRAS and PIK3CA , are central to understand this type of tumor since they highlight broader tumorigenic processes across OC [ 23 , 24 ]. In fact, beyond their known role in double-strand DNA break repair pathways and in particular in the regulation of HR, these mutations also have other functions such as being a regulator of oxidative stress and cell cycle progression ( BRCA1 ) or being involved in transcriptional regulation ( BRCA1/2 ) [ 25 , 26 ].…”

The Molecular Detection of Germline Mutations in the BRCA1 and BRCA2 Genes Associated with Breast and Ovarian Cancer in a Romanian Cohort of 616 Patients

“…Patients with this subtype of ovarian cancer who are negative for somatic mutations of the BRCA1 and BRCA2 genes will be subsequently tested for HRD (Homologous Recombination Deficiency) score evaluation. If the HRD score is positive, these patients could benefit from targeted therapies, such as PARP (poly (ADP-ribose) polymerases) inhibitors (PARPi) [9,10]. Some of the major risk factors for developing breast or ovarian cancer consist of a family history of different types of cancer, the use of estrogen and progesterone replacement therapies, advanced age at first birth, exposure to radiation or other toxic environmental factors, and an unbalanced diet and lack of physical activity [11][12][13][14].…”

“…These estimated lifetime risks may differ according to the location or type of mutation [15]. Carriers of BRCA2 mutations have a 45-69% risk of developing breast cancer, an 11-17% risk of developing ovarian cancer, and a 27-60% risk for males of developing prostate cancer, as well as a higher BRCA1 risk of 6-8% for males of developing breast cancer and a 3-5% risk of developing pancreatic cancer [10,16,17].…”