BRCA and Early Events in the Development of Serous Ovarian Cancer

Abstract

Women who have an inherited mutation in the BRCA1 or BRCA2 genes have a substantial increased lifetime risk of developing epithelial ovarian cancer (EOC), and epidemiological factors related to parity, ovulation, and hormone regulation have a dramatic effect on the risk in both BRCA mutation carriers and non-carriers. The most common and most aggressive histotype of EOC, high-grade serous carcinoma (HGSC), is also the histotype associated with germline BRCA mutations. In recent years, evidence has emerged indicating that the likely tissue of origin of HGSC is the fallopian tube. We have reviewed, what is known about the fallopian tube in BRCA mutation carriers at both the transcriptional and translational aspect of their biology. We propose that changes of the transcriptome in BRCA heterozygotes reflect an altered response to the ovulatory stresses from the microenvironment, which may include the post-ovulation inflammatory response and altered reproductive hormone physiology.

Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry

“…Epithelial ovarian cancer (EOC) is a heterogeneous disease with distinct epidemiological, phenotypical, and molecular subtypes including high-grade serous carcinoma (HGSC), low-grade serous, mucinous, endometrioid, and clear cell carcinoma [1]. Genetically complex and unstable HGSC is the most prevalent histotype and responsible for the highest mortality associated with EOC [1].…”

miR-214-mediated downregulation of RNF8 induces chromosomal instability in ovarian cancer cells

“…19,20 However, the underlying mechanism leading to CIN in ovarian cancer is still poorly understood except that germ line associated BRCA1 or BRCA2 mutations can cause a variety of cancer-prone chromosomal instability syndromes. 21,22 Recently, miR-214 overexpression has been reported in many ovarian cancer tissues. [31][32][33] The magnitude of miR-214 overexpression correlates with ovarian cancer progression 34,35 and CIN is considered to be an early event that drives this progression.…”

“…19,20 Germline-associated BRCA1 or BRCA2 mutations can only be found in a small proportion of ovarian cancers. [21][22][23][24] Even loss of BRCA1 or BRCA2 function due to genetic or epigenetic processes only accounted for a small proportion of ovarian cancers. 25 Somatic mutations or epigenetic alterations in genes for chromosomal instability need to be further discovered.…”

Efficacy of Lycium barbarum polysaccharide and synergism with paclitaxel/cisplatin in ovarian cancer in mice

“…In the United States of America, more than 63 % of women with cancer of the ovaries died in 2015 [1]. Approximately 1.5 % of women may come down with epithelial ovarian cancer (EOC) at one point or the other, a serious statistic due to the fact that this form of ovarian cancer ranks amongst the leading causes of cancer-induced fatalities in women [2].…”