Low Grade Serous Ovarian Carcinoma: From the molecular characterization to the best therapeutic strategy

Pepa, Chiara Della; Tonini, Giuseppe; Santini, Daniele; Losito, Simona; Pisano, Carmela; Napoli, Marilena Di; Cecere, Sabrina Chiara; Gargiulo, Piera; Pignata, Sandro

doi:10.1016/j.ctrv.2014.12.003

Cited by 80 publications

(48 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies support a fallopian tube origin for high grade serous cancers, especially in women who carry a hereditary mutation in BRCA genes(3). Low grade serous cancers may arise in stepwise fashion from fallopian tube fimbriae or ovarian surface epithelium(4). Endometrioid cancers may arise from endometrial surface epithelium shed in retrograde fashion onto the ovaries and peritoneal tissue(5).…”

Section: Introductionmentioning

confidence: 99%

Characterization of ovarian cancer cell lines as in vivo models for preclinical studies

Hernandez

Kim

Lyle

et al. 2016

Gynecologic Oncology

View full text Add to dashboard Cite

Objective The value of cell lines for pre-clinical work lies in choosing those with similar characteristics. Selection of cell lines is typically based on patient history, histological subtype at diagnosis, mutation patterns, or signaling pathways. Although recent studies established consensus regarding molecular characteristics of ovarian cancer cell lines, data on in vivo tumorigenicity remains only sporadically available, impeding translation of in vitro work to xenograft models. Methods We introduced 18 ovarian cancer cell lines into athymic nude mice through subcutaneous, intraperitoneal, and ovary intrabursal routes, and observed tumor development over 6 weeks. We also profiled cell line gene expression and identified differentially expressed gene sets based on their ability to form tumors in the subcutaneous or intraperitoneal locations. Representative cell lines were further subjected to proteomic analyses. Results Ovarian cancer cell lines showed variable ability to grow in mice when implanted subcutaneous, intraperitoneal, or intrabursal. While some cell lines grew well in both SC and IP locations, others showed a strong propensity to grow in one location only. Gene expression profiles suggested that cell lines showing preference for IP growth had gene expression patterns more similar to primary tumors. Conclusions We report the tumorigenicity of 17 human ovarian cancer cell lines and one mouse cell line in three distinct anatomical locations, and associated gene networks. Growth patterns and histopathology, linked to molecular characteristics, provide a valuable resource to the research community, and better guide the choice of cell lines for in vitro studies to translate efficiently into xenograft testing.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterization of ovarian cancer cell lines as in vivo models for preclinical studies

Hernandez

Kim

Lyle

et al. 2016

Gynecologic Oncology

View full text Add to dashboard Cite

show abstract

“…Each epithelial ovarian cancer histologic subtype exhibits a distinct etiologic and molecular pathogenesis and sensitivity to treatment (e.g., chemotherapeutic agents) (Anglesio et al 2013; Della Pepa et al 2015; Risch et al 1996; Shih Ie and Kurman 2004; Soslow 2008). It has been suggested that serous carcinomas arise from the epithelial mucosal lining of the fallopian tube fimbriae or from endosalpingiotic deposits on the ovarian or peritoneal surfaces.…”

Section: Introductionmentioning

confidence: 99%

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Cuéllar-Partida¹,

Lu²,

Dixon³

et al. 2016

Hum Genet

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ( hg2=8.8±1.10.16667em%), endometrioid ( hg2=3.2±1.60.16667em%), clear cell ( hg2=6.7±3.30.16667em%) and all EOC ( hg2=5.6±0.60.16667em%). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.

show abstract

“…The high-grade OSC originates de novo from intraepithelial carcinoma in ovarian surface inclusion cysts or from fallopian tube epithelium. In support of a dualistic pathway are molecular genetic differences between low-grade and high-grade OSC with frequent mutations of KRAS and BRAF and infrequent p53 mutations in low-grade OSC, the converse being the rule in high-grade OSC 3 7. The two-tier system was initially proposed based on morphological and molecular genetic features and was subsequently shown in a multivariate analysis to be useful in predicting outcome.…”

Section: Introductionmentioning

confidence: 99%

Expression of EphB6 in ovarian serous carcinoma is associated with grade, TNM stage and survival

Ning

et al. 2015

J Clin Pathol

View full text Add to dashboard Cite

show abstract

Low Grade Serous Ovarian Carcinoma: From the molecular characterization to the best therapeutic strategy

Cited by 80 publications

References 62 publications

Characterization of ovarian cancer cell lines as in vivo models for preclinical studies

Characterization of ovarian cancer cell lines as in vivo models for preclinical studies

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Expression of EphB6 in ovarian serous carcinoma is associated with grade, TNM stage and survival

Contact Info

Product

Resources

About